Term
| What is most abundant in cell membrane? |
|
Definition
|
|
Term
| What is the cell membrane made of? |
|
Definition
|
|
Term
| What does amphipathic mean? |
|
Definition
| Containing polar and nonpolar regions. |
|
|
Term
| What does cholesterol do? |
|
Definition
| It stiffens membranes and decreases membrane permeability to small water soluble molecules. |
|
|
Term
|
Definition
| Negatively charged ones increase the concentration of cations at the membrane surface; some act as receptors for bacterial toxins. |
|
|
Term
| What does it mean that the lipid distribution in bilayer is asymmetric? |
|
Definition
| glycolipids and choline-containing phospholipids only present on non-cytoplasmic side of membrane while phospholipids with terminal primary amine group are on cytoplasmic surface. |
|
|
Term
| Name the different type of membrane proteins. |
|
Definition
| Integral proteins, peripheral proteins, glycoproteins. |
|
|
Term
| Name some functions of integral proteins. |
|
Definition
| receptors, pores, channels, carriers, enzymes, adhesion molecules, intracellular signalling. |
|
|
Term
| What are peripheral proteins used for? |
|
Definition
| The formation of a submembranous cytoskeleton. |
|
|
Term
| What are glycoproteins involved with? |
|
Definition
| cell-cell interactions, receptors for viruses, antigenic determinants, cell surface negativity. |
|
|
Term
|
Definition
| carbohydrate rich coating of cells formed by glycolipids and glycoproteins. |
|
|
Term
| What is the function of the glycocalyx? |
|
Definition
| protect cell from mechanical and chemical damage; enables cells to identify and interact with one another. |
|
|
Term
| Are lipids and proteins mobile in cell membrane? |
|
Definition
| Yes. Can freely move in the plane of the membrane. |
|
|
Term
| What are the functions of biological membranes? |
|
Definition
| permeability barrier for water-soluble substances, forms cell organelles, and packages and transports materials within cells. |
|
|
Term
|
Definition
| uptake of extracellular material in membrane bound vesicles. requires energy. |
|
|
Term
|
Definition
| a triggered process; uptake of large particulate matter; first bind to receptors on cell surface; vesicles are large; only some cells capable of it (e.g. macrophages and neutrophils) |
|
|
Term
| What are the receptors for phagocytosis? |
|
Definition
| Fc receptors for Fc portion of antibodies bound to pathogens, complement receptors, receptors that recognize oligosaccharides on surface of some microoorganisms, and presence of phosphatidylserine on apoptotic cells triggers phagocytosis. |
|
|
Term
|
Definition
| fluid filled endocytosis, a non-triggered process.; occurs at membrane sites coated with clathrin; constitutive process occuring in almost all cells; vesicles are small. |
|
|
Term
| What is receptor-mediated endocytosis? |
|
Definition
| uptake of specific substances bound to membrane receptors.; receptors gather in clathrin coated regions (coated pits), go through endocytosis, lose clathrin coat and ligand is released. |
|
|
Term
| What is caveolae endocytosis? |
|
Definition
| clathrin-independent endocytosis; small invaginations of ell membrane called caveolae occur at membrane sites rich in cholesterol and sphingomyelin (lipid rafts) which contain caveolin; caveolae pinch off to make vesicle and transport large molecules to plasma membrane on other side of cell = transcytosis. |
|
|
Term
|
Definition
| Discharge of intracellular materials contained in membrane-bound vesicles. requires energy. primary method by which neurotransmitters, hormones, etc. are secreted. |
|
|
Term
|
Definition
| movement of atoms, molecules, or ions from one location to another as a result of their random, thermal motion. |
|
|
Term
|
Definition
| movement of a substance from a region of higher concentration to region of lower concentration as a result of random movement. |
|
|
Term
| Explain Fick's first law of diffusion. |
|
Definition
| in a continuous system, the rate of diffusion across a planar surface is directly proportional to the area of the plane and the concentration gradient across the plane. |
|
|
Term
| Explain the Fick equation. |
|
Definition
| J = -DA (dc/dx), where J = net rate of diffusion in moles or grams per unit time; A = area of the plane; dc/dx = concentration gradient across the plane; D = diffusion coefficient |
|
|
Term
| What is the diffusion coefficient proportional to? |
|
Definition
| The speed at which a substance moves through the surrounding medium. |
|
|
Term
| At a small distance, diffusion is what? |
|
Definition
|
|
Term
| When diffusing molecules don't interact with the barrier, describe the Fick equation. |
|
Definition
| J = -DA(change in C)/(change in X), where change in C = the concentration gradient across the barrier, and change in X = thickness of the barrier. |
|
|
Term
| What is one of the most important factors that determines how quickly a substance will move across cell membranes? |
|
Definition
|
|
Term
| What is the partition coefficient? |
|
Definition
| That which measures the lipid solubility of a substance: Bi = [i]oil/[i]water, where Bi = partition coefficient of i, [i]oil = concentration of i in oil, [i]water = concentration of i in water. |
|
|
Term
| What are the properties of water? |
|
Definition
| distilled water is 55.55 molar; solute molecules displace water molecules and decrease water concentration; water tends to flow from region of high water concentration (low solute) to regions of low water concentration (high solute). |
|
|
Term
|
Definition
| the number of osmotically active particles in a solution? for salts, dissociation must be taken into account. |
|
|
Term
|
Definition
| The number of osmoles/liter of solution. |
|
|
Term
|
Definition
| The number of osmoles/kg of water. |
|
|
Term
|
Definition
| The movement of water across a semipermeable membrane down its concentration gradient. |
|
|
Term
| What is osmotic pressure created by? |
|
Definition
| The difference in the concentration of impermeant substances across a semipermeable membrane. |
|
|
Term
| What is osmotic pressure? |
|
Definition
| That pressure which just counterbalances the movement of water into the solution. |
|
|
Term
| What does the osmotic pressure depend on? |
|
Definition
| the number of solute particles present. |
|
|
Term
| Name some colligative properties. |
|
Definition
| Osmotic pressure, freezing point depression, vapor pressure depression and boiling point elevation. |
|
|
Term
|
Definition
| osmotic pressure = RTnc, where R = ideal gas constant (0.0821 atm*K-1mole-1), T = absolute temperature (K), c = molar concentration of solute (moles of solute/liter) and n = number of particles formed by dissociation of a solute molecule. |
|
|
Term
| Compare osmotic pressures. |
|
Definition
| Equal = isosmotic; higher = hyperosmotic; lower = hypoosmotic. |
|
|
Term
|
Definition
| A solution's ability to influence the volume of cells immersed in it. |
|
|
Term
| Why is cell volume only a reflection of the concentration of solutes in the extracelular solution compared with the solute concentration intracellularly? |
|
Definition
| Plasma membranes are relatively impermeable to most biological solutes but highly permeable to water. |
|
|
Term
| Compare the tonicity of solutions. |
|
Definition
Isotonic = equal
Hypertonic = higher; cell shrinks
Hypotonic = lower; cell swells and lyses |
|
|
Term
| What happens when you add permeant solutes to physiological solutions? |
|
Definition
| Only transient change in cell volume occur. |
|
|
Term
| What happens when you place cells in solutions with only permeant solutes? |
|
Definition
|
|
Term
| What is the reflection coefficient? |
|
Definition
| the measure of the permeability of a membrane to a solute. |
|
|
Term
| What is the range of the reflection coefficient and what does it mean? |
|
Definition
| 0 to 1; 0 = extremely permeable; 1 = impermeable |
|
|
Term
|
Definition
| Movement of ions, molecules and particles in the same direction as a result of some force acting on them. |
|
|
Term
| Give an example of bulk flow. |
|
Definition
| Blood flow within blood vessels. |
|
|
Term
|
Definition
| Separation by size, of solutes achieved by forcing the solution through a filter. |
|
|
Term
| Where does ultrafiltration occur? |
|
Definition
|
|
Term
| What is carrier mediated transport? |
|
Definition
| Movement of substances across the plasma membrane by protein carrier molecules (integral membrane proteins). |
|
|
Term
| Explain the model of carrier mediated transport. |
|
Definition
Molecule can't cross or crosses membrane very slowly.
Carrier molecules have site which specifically binds molecule.
Molecule binding to site promotes conformational change, molecule is transported. No channel made. |
|
|
Term
|
Definition
| When the rate of transport reaches its maximum as the concentration of transported substance increases; due to fixed and limited number of transporters in membrane. |
|
|
Term
| What are the properties of mediated transport? |
|
Definition
| Saturation, specificity and competition. |
|
|
Term
|
Definition
| Each carrier molecule binds to only a select group of substances but it's not absolute. |
|
|
Term
|
Definition
| Since specificity isn't absolute, structurally related molecules can compete for transporter, decreasing rate of transport. |
|
|
Term
| What can inhibit transport? |
|
Definition
| Substances not structurally related to transported ion or molecule. |
|
|
Term
| Give an example of inhibition. |
|
Definition
| ATPases are inhibited by metabolic poisons that stop production of ATP. |
|
|
Term
| What is facilitated diffusion? |
|
Definition
| Protein carrier-mediated transport of substances down a concentration gradient; bidirectional. |
|
|
Term
| What is active transport? |
|
Definition
| Protein carrier-mediated transport of substances against a gradient; requires energy; unidirectional. |
|
|
Term
| What are the types of active transport? |
|
Definition
|
|
Term
| Expplain primary active transport. |
|
Definition
| ATP hydrolysis supplies energy to transporter. |
|
|
Term
| Give an example of primary active transport. |
|
Definition
|
|
Term
| Explain secondary active transport. |
|
Definition
| Energy for transport isn't provided directly by ATP hydrolysis by indirectly by using existing gradient of an ion (Na). |
|
|
Term
|
Definition
| Transporter that transports only one substance at a time. |
|
|
Term
| Give an example of a uniport. |
|
Definition
| Facilitated diffusion of glucose. |
|
|
Term
|
Definition
| Symport transport; carrier has at least two sites; can transport substances in same direction. |
|
|
Term
| What transporters use cotransport and countertransport? |
|
Definition
| Secondary active transporters. |
|
|
Term
| Give an example of cotransport. |
|
Definition
| Na cotransport of amino acids. |
|
|
Term
| What is countertransport. |
|
Definition
| Antiport exchangers; carrier has at least two sites; all sites must be occupied; substances move in opposite directions. |
|
|
Term
| Give an example of countertransport. |
|
Definition
|
|
Term
|
Definition
| Present to help maintain low levels of intracellular free Ca. |
|
|
Term
| What are the type of Ca pumps? |
|
Definition
|
|
Term
|
Definition
| Sarcoplasmic and Endoplasmic Reticulum Calcium ATPases; located on membranes of intracellular organelles; actively sequester Ca in intracellular stores. |
|
|
Term
|
Definition
| Plasma Membrane Calcium ATPases; play a major role in maintaining low intracellular Ca; inactive at physiologic [Ca], but when [Ca] increases, calcium combines with calmodulin (CaM) and that binds to pumpk, icnreasing affinity for Ca, as [Ca] decreases, Ca and CaM dissociate and pump is inactive. |
|
|
Term
|
Definition
| Occurs in parietal cells of gastric mucosa; transporter is H-K ATPase which transports H into gastric lumen and K into pareital cell. |
|
|
Term
| What do anion exchangers do? |
|
Definition
| Exchange extracellular univalent anions for intracellular ones. |
|
|
Term
| Give an example of an anion exchanger. |
|
Definition
| Chloride-bicarbonate exchanger. |
|
|
Term
| Explain Na-K-2Cl transporter. |
|
Definition
| Found in variety of nonepithelial cells and basolateral membrane of some epithelial cells; one function is regulation of cell volume. |
|
|
Term
| What are ABC transporters? |
|
Definition
| ATP-Binding Cassette transporters; all bind ATP, some act as primary active transporters, some hydrolyze ATP but don't use energy for transport, and in others, ATP binding regulates ion exchange. |
|
|
Term
| Explain the ABC1 subfamily of ABC transporters? |
|
Definition
| Involved in transport of phospholipids and cholesterol out of macrophages. |
|
|
Term
| Explain MDR subfamily of ABC transporters? |
|
Definition
| Multidrug resistant transporters; primary active transporters that remove cationic drugs and metabolites from cells; found in wide variety of cells; clinically important. |
|
|
Term
| Explain CFTR subfamily of of ABC transporters. |
|
Definition
| Cystic fibrosis transmembrane regulator; Cl channel found in apical membrane of many epithelial cells; ATP regulates functioning of this channel. |
|
|
Term
| How does ATP regulate functioning of Cl channel? |
|
Definition
| Channel has regulatory domain with site that must be phosphorylated for channel funciton; channel has two nucleotide binding domains to which ATP must bind for channel funciton. |
|
|
Term
| What are tight junctions? |
|
Definition
| Very close appositions of adjacent cell membranes; form relatively impermable barriers to movement of substances between cells. |
|
|
Term
| What do tight junctions demarcate? |
|
Definition
| The boundary between the apical and basolateral membranes of the epithelial cells. |
|
|
Term
| Where does the apical membrane lie? |
|
Definition
| On luminal side of tissue. |
|
|
Term
| Where is the basolateral membrane? |
|
Definition
| On the serosal or peritubular side. |
|
|
Term
| Explain how epithelial cells are polarized. |
|
Definition
| Complement of transport proteins on apical membrane differs from that on the basolateral membrane; no individual transport protein is found in both membranes; asymmetry allows unidirectional transport of substances across the epithelium. |
|
|
Term
| How are some tight junctions "leaky"? |
|
Definition
| Relatively permeant to ions and water; allows for transport of isosmotic solutions. |
|
|
Term
| Give an example of where "leaky" tight junctions are located. |
|
Definition
|
|
Term
| Explain impermeant tight junctions. |
|
Definition
| They bloc ion diffusion, function to maintain large transepithelial ion or osmotic gradients. |
|
|
Term
| Explain the properties common to most epithelia. |
|
Definition
| Na-K pump located on basolateral membrane; most K taken up by Na-K pump leaves cell through K channels in basolateral membrane; Na is lower intracellularly than extracellularly. |
|
|
Term
| Where is the Na-K pump not located on basolateral membrane? |
|
Definition
|
|
Term
| What are the two pathways for transepithelial transport? |
|
Definition
| Transcellular pathway and paracellular pathway. |
|
|
Term
| Explain the transcellular pathway. |
|
Definition
| Substances must cross apical membrane, cytoplasm and basolateral membrane of an epithelial cell. |
|
|
Term
| Explain the paracellular pathway. |
|
Definition
| Substance moves between epithelial cells through the tight junctions and into the lateral intracellular space. |
|
|
Term
| What is the general mechanism for the transcellular pathway? |
|
Definition
| Substance is actively transported in or out on one side of the cell and leaves or enters the other by a passive process (diffusion or facilitated diffusion). |
|
|
Term
| What is the general mechanism for the paracellular pathway? |
|
Definition
| Ions or water move through tight junctions between cells in response to electrical or chemical gradients (ions) or osmotic gradients (water). |
|
|
Term
| Explain glucose transport in small intestine. |
|
Definition
| Glucose enters cell at luminal border via Na-gradient driven secondary active transport, diffuses across cell cytoplasm; leaves cell at basolateral membrane via facilitated diffusion. |
|
|
Term
|
Definition
| Basolateral Na-K pump keeps intracellular Na concentration low, creating a large electrochemical gradient for Na entry; Na channels in apical membrane allow Na to move down gradient into cell; Na that enters is pumped out across basolateral membrane; since Na-K pump creates a net positive charge from lumen to interstitium, Cl moves from lumen to interstitium through paracellular pathway; net result is NaCl absorption in collecting tubule of kidney. |
|
|
Term
|
Definition
| If apical surface of epithelial cells also contain K channels in addition to Na channels, then some of K that's taken up by Na-K pump can be secreted across apical membrane; mechanism used by the collecting tubule of kidney to secrete it. |
|
|
Term
| What is standing gradient osmosis? |
|
Definition
| One of several methods by which epithelial cells transport water and electrolytes. |
|
|
Term
| Where is standing gradient osmosis used? |
|
Definition
| By epithelial cells of gall bladder to concentrate bile. |
|
|
Term
| Explain the model of standing gradient osmosis. |
|
Definition
a. Na actively pumped into intercellular spaces.
b. electrical potential created by Na transport draws Cl (and HCO3) into intercellular space.
c. solution in lateral intercellular space becomes hyperosmotic
d. osmotic flow of water occurs into intercellular space from lumen and through surrounding cells.
f. by the time solution reaches serosal border, it's nearly isotonic. |
|
|
Term
| Why is ion diffusion through lipid limited? |
|
Definition
| Lipid is non-polar and doesn't accomodate charged particles; lipid bilayer is virtually impermeable to ions. |
|
|
Term
| Most ion channels have what? |
|
Definition
|
|
Term
| What is a selectivity filter? |
|
Definition
| A narrow region of a channel that contains a charged site. |
|
|
Term
| What factors can determine how one ion can be selected over another? |
|
Definition
| Size, site strength, and channel configuration. |
|
|
Term
| Most channels exist in what state under resting conditions? |
|
Definition
|
|
Term
| What are voltage-gated channels? |
|
Definition
| A channel in which the probability of opening is increased by voltage change across a membrane. |
|
|
Term
| Give an example of voltage-gated channels. |
|
Definition
| Voltage-gated Na channels. |
|
|
Term
| What are ligand-gated ion channels? |
|
Definition
| Channels that respond to extracellularly applied chemicals. |
|
|
Term
| Give an example of a ligand-gated ion channel. |
|
Definition
| Acetylcholine-receptor channel. |
|
|
Term
| What are messenger-activated channels? |
|
Definition
| Channels which respond to intracellular messengers. |
|
|
Term
| Give an example of messenger-activated ion channels. |
|
Definition
| ACh activated K channels of heart. |
|
|
Term
| What are stretch-activated channels? |
|
Definition
| Channels which open in response to stretch. |
|
|
Term
| Give an example of stretch-activated channels. |
|
Definition
|
|
Term
| Explain asymmetry of ion distribution across cell membrane. |
|
Definition
| [K]i > [K]o; [Na]i < [Na]o; [Cl]i < [Cl]o; [Ca]i << [Ca]o; [Mg]i = [Mg]o |
|
|
Term
| What role do impermeant, intracellular anions play in the cell? |
|
Definition
| They're part of the negative charge in cell interior but don't contribute directly to membrane potential; increase intracellular osmotic pressure. |
|
|
Term
| What are the forces action on ions? |
|
Definition
| Chemical gradients and electrical gradients. |
|
|
Term
| What does the Nernst Equation describe? |
|
Definition
| The potential across a membrane that will produce an electrical force equal and opposite to the chemical force produced by the difference in concentration of the ion across the membrane; refers to potential inside cell. |
|
|
Term
| What is the Nernst Equation? |
|
Definition
| Ex = (RT/ZF)ln([X]o/[X]i); Ex = equilibrium potential for ion X, R = gas constant; T = absolute temperature; ln = natural log; z = valence of ion X; F = Faraday's number; [X]o = external concentration of X, [X]i = internal concentration of X. |
|
|
Term
| What is the Nernst Equation at 37 Celsius and in log10 scale? |
|
Definition
| Ex = (60/Z)log10([X]o/[X]i) |
|
|
Term
| What is membrane potential? |
|
Definition
| The electrical potential difference between the inside and outside of most cells; also known as resting potential or Em. |
|
|
Term
| Describe the Em inside the cell. |
|
Definition
| It's negative and ranges from a few mVs to about -100 mV. |
|
|
Term
| The magnitude of the membrane potential is determined by what? |
|
Definition
| The distribution of ions across the membrane and the permeability of the membrane to those ions. |
|
|
Term
| In excitable cells, what ion is most permeable? |
|
Definition
|
|
Term
| What accounts for deviation of membrane potential from the theoretical value? |
|
Definition
| Small permeability to Na. |
|
|
Term
|
Definition
|
|
Term
| How large is the contribution of other ions on Em? |
|
Definition
|
|
Term
| A steady membrane potential is obtained only when there is what? |
|
Definition
|
|
Term
| Explain how Na and K are out of electrochemical balance. |
|
Definition
| Na has large gradient driving it in but small conductance; K has small gradient driving it out but there is high conductance. |
|
|
Term
| Explain how Na and K are out of electrochemical balance. |
|
Definition
| Na has large gradient driving it in but small conductance; K has small gradient driving it out but there is high conductance. |
|
|
Term
| How is the ion flux balanced out? |
|
Definition
| At rest, efflux of K and influx of Na balance each other out via passive diffusion (or they would if there were no other forces involved). |
|
|
Term
| What is the function of the Na-K ATPase? |
|
Definition
| Maintaining the electrical and chemical gradients. |
|
|
Term
| What does the Na-K ATPase do? |
|
Definition
| It moves three Na out of cell and two K into cell; creates a membrane potential that's more negative than what would be achieved by passive diffusion; Na-K pump balances gradients out so that there is no net ion flux. |
|
|
Term
| Is the membrane potential in equilibrium? |
|
Definition
|
|
Term
| What happens during depolarization? |
|
Definition
| Em becomes less negative. |
|
|
Term
| What happens during hyperpolarization? |
|
Definition
| Em becomes more negative. |
|
|
Term
| Biological membranes act like what? |
|
Definition
| Resistors and capacitors in parallel. |
|
|
Term
| Why does it take time for the membrane potential to change in response to an applied current? |
|
Definition
| The capacitance of the membrane. |
|
|
Term
| The larger the membrane capacitance, the ________ it will take the potential to reach final level. |
|
Definition
|
|
Term
| What does the time constant describe? |
|
Definition
| The time course of the potential change. |
|
|
Term
| What is the time constant for a spherical cell? |
|
Definition
| time constant = RmCm = t; where t = time it takes for potential to rise to a value of 1 - 1/e (67%) or fall to a value of 1/e (37%) of its peak value; Rm = resistance of cm2 of membrane; Cm = capacitance of cm2 of membrane. |
|
|
Term
| What happens during graded potentials? |
|
Definition
| The amplitude varies with stimulus intensity. |
|
|
Term
| What is electrotonic conduction? |
|
Definition
| Decremental conduction; when away from site of stimulus application, response is smaller and slower. |
|
|
Term
| What will determine how final amplitude of a potential varies with distance away from its site of origin? |
|
Definition
|
|
Term
| What is the length constant? |
|
Definition
| The distant at which a potential has fallen to 37% (1/e) of its original value; length constant = square root of rm/ri, where rm = transmembrane resistance per unit length and ri = axial, longitudinal, resistance per unit length of cytoplasm; therefore the larger rm or smaller ri, the longer the length constant. |
|
|
Term
| What is an action potential? |
|
Definition
| A large, self-sustaining potential charge; propagated without decrement away from the site of stimulus application. |
|
|
Term
|
Definition
| The value of Em at which a cell produces an action potential. |
|
|
Term
| What is ionic conductance? |
|
Definition
| The inverse of resistance. |
|
|
Term
| What affects ionic conductance? |
|
Definition
| The higher the resistance, lower the conductance; greater number of channels open, higher the conductance. |
|
|
Term
| How are action potentials possible? |
|
Definition
|
|
Term
| What causes voltage-gated Na channels to open? |
|
Definition
|
|
Term
| What causes depolarization? |
|
Definition
| Na moves into cell down its electrochemical gradient. |
|
|
Term
| What happens when voltage-gated Na channels inactivate? |
|
Definition
| Na entry declines and membrane potential begins to return to resting level. |
|
|
Term
| What opens voltage-gated K channels? |
|
Definition
| Depolarization after a slight delay. |
|
|
Term
| What happens when voltage-gated K channels open? |
|
Definition
| K leaves cell, leading to repolarization. |
|
|
Term
| At what speed do voltage-gated K channels close? |
|
Definition
| Slowly, leading to hyperpolarization thanks to increased K conductance. |
|
|
Term
|
Definition
| The potential at which positive inward current just exceeds the countervailing outward current and thus sets off the positive feedback loop. |
|
|
Term
| What factors effect threshold? |
|
Definition
| Density of Na channels, availability of Na channles that can be activated, concentration of divalent cations after threshold (e.g. Ca). |
|
|
Term
| What happens to threshold in hypocalcemia? |
|
Definition
| It moves closer to resting membrane potential leading to hyperexcitablility and spontaneous muscle contractions. |
|
|
Term
| What happens to threshold in hypercalcemia? |
|
Definition
| It moves further away from resting potential, leading to hypoexcitability and muscle weakness. |
|
|
Term
| What is the refractory period? |
|
Definition
| The period of time during or after an action potential in which it is either not possible or its more difficult to generate another action potential. |
|
|
Term
| What happens during the absolute refractory period? |
|
Definition
| No matter how strong the stimulus, an additional action potential can be produced, mostly due to Na channel inactivation. |
|
|
Term
| What happens during the relative refractory period? |
|
Definition
| Second action potential can be generated but a stronger stimulus is necessary, due to an elevated permeability of K (gK). |
|
|
Term
| What happens during accomodation? |
|
Definition
| During a slow depolarization, threshold can be exceed without trigguring action potential; produced by Na channel inactivation and increased gK. |
|
|
Term
| What is the all-or-none response? |
|
Definition
| A stimulus either fails to elicit an action potential or it produces on in full-size; doesn't mean that all action potentials are same amplitude. |
|
|
Term
| When do action potentials not have same amplitude? |
|
Definition
| Relative refractory period. |
|
|
Term
|
Definition
| Peak potential exceeds - mV, cell polarity is reversed; caused by Em approaching Ena and/or Eca. |
|
|
Term
| Name some variations to normal action potentials. |
|
Definition
| Cardiac and smooth muscle action potentials. |
|
|
Term
| Describe cardiac action potentials. |
|
Definition
| Initial fast rising phase due in part to fast Na channels; prolonged plateau phase in part to slow, L-type Ca channel; repolarization due to closing slow channels and much delayed reopening of K channels. |
|
|
Term
| Describe smooth muscle action potentials. |
|
Definition
| Longer duration than skeletal muscle action potential; rising phase due to slow, L-type Ca channels (sometimes Na channels); repolarization due to closing of slow channels and opening of K channels. |
|
|
Term
| What alters activity of voltage-gated Na channels? |
|
Definition
| Neurotoxins and local anesthetic. |
|
|
Term
| What toxins block voltage-gated Na channels? |
|
Definition
| Tetrodotoxin (TTX, from puffer fish), saxitoxin (STX, dinoflagellates), u-canotoxin (from marine snail; only blocks Na channels in skeletal muscle). |
|
|
Term
| What local anesthetics block voltage-gated Na channels? |
|
Definition
| Cocaine, procaine, lidocain, tetracaine. |
|
|
Term
| How do toxins promote Na channel activity? |
|
Definition
| They produce both a longer duration of channel opening and enhanced opening under voltage conditions in which channels are usually closed or inactivated. |
|
|
Term
| What are specific neurotoxins that promote Na channel activity? |
|
Definition
| Batrachotoxin (from tropical frogs), veratridine (from plant alkaloids), pyrethrins (from natural plant insecticides), and brevetoxins (from dinoflagellates). |
|
|
Term
| What are the four major types of voltage-gated K channels? |
|
Definition
| Delayed outward rectifiers, inward rectifiers, transiet outward rectifiers, and Ca-activated K currents. |
|
|
Term
| Explain delayed outward rectifiers. |
|
Definition
| Slow to activate in response to depolarization; allows outward movement of K, inactivates slowly, blocked by tetraethylammonium (TEA). |
|
|
Term
| Explain inward rectifiers. |
|
Definition
| Also known as anomalous rectifiers; allow inward movement of K but little outward movement at depolarization; prevent excessive loss of K, blocked by tertiapin. |
|
|
Term
| Explain transient outward rectifiers. |
|
Definition
| Activate and inactivate rapidly, activate at more negative channels than other K channels, activated during the afterhyperpolarization phase in some neurons and can control rate of spontaneous action potential discharge; blocked by 4-aminopyridine. |
|
|
Term
| Explain Ca-activated K currents. |
|
Definition
| Very common type in various tissues; depolarization on increased intracellular Ca opens them; blocked by Apamin adn Charybdotoxin. |
|
|
Term
| What does conduction velocity depend on? |
|
Definition
| Rate of electrotonic current spread down fiber away from active site. |
|
|
Term
| Electrotonic conduction is rate-liming factor in what? |
|
Definition
| The speed of propagation of the action potential. |
|
|
Term
| The larger the fiber diameter, the ______ the axial resistance and the _______ the current will spread. |
|
Definition
|
|
Term
| The smaller the capacitance, the ________ the segment of axon will be depolarized, the _______ the current will spread. |
|
Definition
|
|
Term
| Conduction velocity is proportional to what? |
|
Definition
| length constant/time constant |
|
|
Term
| Explain conduction in muscle of unmyelinated nerves. |
|
Definition
| Na entering active region depolarizes adjacent region of plasma membrane, causing region to reach threshold; action potentials are produced in consecutive adjacent regions down nerves or muscle. |
|
|
Term
| What do Schwann cells and oligodendrocytes do? |
|
Definition
| Wrap around nerve fibers forming covering (myelin). |
|
|
Term
| Each Schwann cell forms how many segments of myelin on one axon? |
|
Definition
|
|
Term
| Does each oligodendrocyte form myelin segments on one or many axons? |
|
Definition
|
|
Term
| What does myelination do? |
|
Definition
| Greatly increases plasma membrane resistance and decreases membrane capacitance. |
|
|
Term
| The increase in membrane resistance leads to what? |
|
Definition
| Increased length constant. |
|
|
Term
| What happens due to decreased capacitance? |
|
Definition
| Internodal membrane depolarizes more rapidly. |
|
|
Term
| What are the nodes of Ranvier? |
|
Definition
|
|
Term
| What is present at the nodes of Ranvier? |
|
Definition
| Many Na channels and very few K channels. |
|
|
Term
| What is the internodal region? |
|
Definition
| The myelinated portion between nodes. |
|
|
Term
| What is present in the internodal region? |
|
Definition
| K channels are localized there, virtually no Na channels. |
|
|
Term
| Action potentials occur where in myelinated nerves? |
|
Definition
|
|
Term
| What is saltatory conduction? |
|
Definition
| The action potentials moving from node to node. |
|
|
Term
| Why are myelinated nerves more energy efficient? |
|
Definition
| Transmembrane currents are restricted to small membrane surface area, fewer can traverse membrane and less pumping is necessary to maintain gradients. |
|
|
Term
| Name some demyelination diseases. |
|
Definition
| Multiple Sclerosis and Guillain-Barre Syndrome. |
|
|
Term
| What is Multiple Sclerosis. |
|
Definition
| Most common demyelination disease of CNS; autoimmune disease; demyelination exposes voltage-gated K channels normally covered, could short circuit action potentials; demyelination also makes K channels accessible to drug therapy. |
|
|
Term
| What is Guillain-Barre Syndrome? |
|
Definition
| Most common demyeliniation disease in PNS; demyelination triggered by viral infection; given proper supportive treatment, most patients recover because PNS has ability to remyelinate itself. |
|
|
Term
|
Definition
| Specialized places where the information contained in the electrical activity of a nerve is transferred to another cell. |
|
|
Term
| What is the presynaptic element? |
|
Definition
|
|
Term
| What is the postsynaptic element? |
|
Definition
|
|
Term
| What is the synaptic cleft? |
|
Definition
| The space between pre- and postsynaptic structures. |
|
|
Term
|
Definition
| The time between arrival of an action potential in the presynaptic neuron and a potential change in the postsynaptic cell. |
|
|
Term
| What types of synapses are there? |
|
Definition
|
|
Term
| What happens at electrical synapses? |
|
Definition
| Communication is by direct passage of current from one cell to another cell. |
|
|
Term
| Describe an electrical synapse. |
|
Definition
| Synaptic cleft is small; pre- and postsynaptic elements connected by gap junctions; virtually no synaptic delay; pre- and postsynaptic elements tend to be equal size; transmission is often bidirectional; uncommon in mammals. |
|
|
Term
| What happens at a chemical synapse? |
|
Definition
| Communication is via a chemical neurotransmitter. |
|
|
Term
| Describe a chemical synapse. |
|
Definition
| Transmitter is contained in vesicles in presynaptic ending; synaptic cleft is large; no electrical connection between pre- and postsynaptic elements; there is a synaptic delay; presynaptic ending often much smaller than postsynaptic cell; postsynaptic cell has neurotransmitter receptors; transmission is unidirectional; most common type of synapse in CNS and PNS. |
|
|
Term
| What is a neuromuscular junction? |
|
Definition
| The synapse between a motor neuron and a skeletal muscle fiber; also called myoneural junction or end plate. |
|
|
Term
| Describe the structure of the nmj. |
|
Definition
| Presynaptic ending, prominent synaptic cleft, postsynaptic cell. |
|
|
Term
| What is in the presynaptic ending at a neuromuscular junction? |
|
Definition
| clear vesicles that contain ACh which accumulate near specialized release sites called active zones which are lined with voltage-gated Ca channels. |
|
|
Term
| Explain the postsynaptic cell at a neuromuscular junction. |
|
Definition
| Muscle membrane under presynaptic ending is thrown into a junctional fold with ACh receptors on peaks which are lined up with active zones; acetylcholinesterase found throughout postsynaptic membrane. |
|
|
Term
| Explain the sequence of events during neuromuscular transmission. |
|
Definition
| Action potential invades presynaptic ending; depolarization opens voltage-gated Ca channels; Ca influx occurs; Ca causes synaptic vesicles to fuse with the plasma membrane and release ACh via exocytosis; ACh diffuses across synaptic cleft and combines with ACh receptors on postjunctional membrane; opening of monovalent cation channels in postjunctional membrane resulting in depolarization called end plate potential (EPP); muscule membrane surrounding end plate gets depolarized, opening voltage-gated Na channels in muscle membrane and action potential is produced which propagates in both directions away from end plate. |
|
|
Term
| What is the end plate potential? |
|
Definition
| Depolarization of the end plate of a neuromuscular junction due to monovalent cation channels being opened. |
|
|
Term
| What has a nearly equal permeability to Na and K? |
|
Definition
|
|
Term
| What happens at the ACh channel? |
|
Definition
| At resting potential, driving force for Na to enter is greater than driving force for K to leave, creates net influx of Na and consequent depolarization; as muscle fiber depolarizes, driving force for K to leave increases and driving force for Na to enter decreases; at some potential (about half way between equilibrium potential for Na and K, in this case), driving forces for ions is equal, no net current through the ACh channel; this is the equilibrium potential, or reversal potential. |
|
|
Term
| Why is the equilibrium potential also called the reversal potential? |
|
Definition
| If the membrane potential exceeds the equilibrium level, the transmitter induced potential reverses polarity (depolarization becomes hyperpolarization). |
|
|
Term
| What is the reversal potential determined by? |
|
Definition
| The permeability change it produces. |
|
|
Term
| Give an example of how the permeability change determines the reversal potential for a transmitter. |
|
Definition
| If a transmitter increases permeability for only one ion, reversal potential will be at the equilibrium potential of the ion; if transmitter increases permeability of more than one ion, its reversal potential will lie somewhere between the equilibrium potential of the ions involved. |
|
|
Term
| What are miniature end-plate potentials (MEPPS)? |
|
Definition
| Small depolarizations that occur at the neuromuscular junction in the absence of nerve stimulation; look and behave like small EPPs. |
|
|
Term
| What is the size of the EPP dependent on? |
|
Definition
| The extracellular Ca concentration. |
|
|
Term
| Describe how [Ca]o influences EPPs. |
|
Definition
| As [Ca]o is reduced (with increase in Mg to maintain divalent ions) EPP become smaller; a point is reached where size of the EPP can no longer be decreased by reducing [Ca]o - nerve stimulation either produces small potential of nothing at all, smallest evoked EPP is MEPP; size of EPP under condition of low extracellular EPP fluctuates but is always some integral multiple of the size of the MEPP. |
|
|
Term
|
Definition
| By the smallest amount of transmitter. |
|
|
Term
| What are the properties of transmitter release at the neuromuscular junction? |
|
Definition
1. each quantum of transmitter contains thousands of molecules of ACh.
2. normally each action potential releases hundreds of quanta.
3. the amount of transmitter released is far in excess of that necessary to produce an action potential in the muscle. |
|
|
Term
| Where is ACh synthesized? |
|
Definition
|
|
Term
|
Definition
| Dietary choline and acetyl CoA. |
|
|
Term
|
Definition
| Taken up into vesicles by specific ACh transport proteins in the vesicle membrane. |
|
|
Term
| How is stored ACh released? |
|
Definition
| In quantal packets (1 vesicle = 1 quanta). |
|
|
Term
| How many molecules of ACh does each vesicle contain? |
|
Definition
|
|
Term
| How many vesicles do presynaptic endings release at a time when done spontaneously? |
|
Definition
|
|
Term
| What results from the spontaneous release of ACh? |
|
Definition
|
|
Term
| How many vesicles of ACh are released during an action potential? |
|
Definition
| Hundreds of vesicles simultaneously. |
|
|
Term
| What results from the vesicle release during an action potential? |
|
Definition
| An EPP that is sufficient enough to exceed threshold and trigger an action potential. |
|
|
Term
| What is the action of ACh at the neuromuscular junction stopped by? |
|
Definition
|
|
Term
| What does AChE hydrolyze ACh into? |
|
Definition
|
|
Term
| What is choline taken up by? |
|
Definition
| The presynaptic ending to make more ACh. |
|
|
Term
| What is the uptake of choline blocked by? |
|
Definition
|
|
Term
| What prevents the hydrolysis of ACh, prolonging its action? |
|
Definition
|
|
Term
| What is myasthenia gravis? |
|
Definition
| an autoimmune disorder in which Ab are produced against nicotinic ACh receptors; nerve terminals are normal but ACh receptors at NMJ are sparse and junctional folds are shallow; 2 major forms of disease (one involves only extraocular muscles, other involves all skeletal muscles especially during the day). |
|
|
Term
| What does the drug treatment for myasthenia gravis involve? |
|
Definition
| Use of cholinesterase inhibitors. |
|
|
Term
| What is Lambert-Eaton syndrome? |
|
Definition
| Patients have Ab against voltage-gated Ca channels in nerve terminals; reduction in Ca influx and consequent reduction in transmitter release; patients exhibit muscular weakness primarily in limb musculature, not ocular muscles. |
|
|
Term
| What percent of patients with Lambert-Eaton syndrome develop or have small cell lung carcinoma? |
|
Definition
|
|
Term
| Lambert-Eaton can appear up to how many years before lung cancer is diagnosed? |
|
Definition
|
|
Term
| What toxins affect the presynaptic action potential? |
|
Definition
| Na channel blockers, K channel blockers, and Ca channel blockers |
|
|
Term
| What do Na channel blockers do? |
|
Definition
| Prevent action potential and inhibit ACh release. |
|
|
Term
| What are examples of Na channel blockers? |
|
Definition
|
|
Term
| What do K channel blockers do to synaptic transmission? |
|
Definition
| Slow repolarization and enhance ACh release by allowing greater Ca influx. |
|
|
Term
| What are some examples of K channel blockers? |
|
Definition
| TEA (tetraethylammonium) and dendrotoxin. |
|
|
Term
| What do Ca channel blockers do to synaptic transmission? |
|
Definition
| Inhibit Ca influx and thereby inhibit release of ACh. |
|
|
Term
| What are some examples of Ca channel blockers? |
|
Definition
| w-canotoxin (maring snail) and some divalent cations (e.g. Co2+). |
|
|
Term
| Name some bacterial toxins that affect synaptic transmission? |
|
Definition
| Botulinum toxin and tetanus toxin. |
|
|
Term
| What does the botulinum toxin do to synaptic transmission? |
|
Definition
| Inhibit transmitter release from cholinergenic endings (both somatic and autonomic) and enters nerve ending and cleaves proteins related to vesicle fusion and exocytosis. |
|
|
Term
| What does the tetanus toxin do to synaptic transmission? |
|
Definition
| Inhibits transmitter release from inhibitory neurons in the spinal cord that normally inhibit muscle contractions by inhibiting alpha motorneurons; toxin enters peripheral nerves and travels to the spinal cord where it eventually ends up in inhibitory interneurons where it exhibits transmitter (glycine) release by cleaving proteins related to vesicle fusion and exocytosis. |
|
|
Term
| Name some agonists of the nicotinic ACh receptor. |
|
Definition
| Carbamylcholine and succinylcholine. |
|
|
Term
| What can carbamylcholine or succinylcholine do to synaptic transmission? |
|
Definition
| Produce flaccid paralysis; activate ACh receptor and are resistant to hydrolysis of AChE, resulting in prolonged opening of the ACh channels and hence a prolonged depolarization of the muscle; initially there's excitation and tremors followed by relaxation due to inactivatin of voltage-gated Na channels in the muscle membrane because of the prolonged depolarization; ACh receptors eventually desensitize, further inhibiting synaptic transmission. |
|
|
Term
| Name an antagonist of the nicotinic ACh receptor. |
|
Definition
|
|
Term
|
Definition
| Causes flaccid paralysis; competitive inhibitor of ACh; binding of curare to ACh receptor doesn't produce depolarization, prevents ACh binding to recepotr, reduces number of receptors available to bind with ACh; inhibition of ACh binding reduces amplitude of EPP to subthreshold levels. |
|
|
Term
| What do inhibitors of AChE do? |
|
Definition
|
|
Term
| What are some examples of reversible inhibitors of AChE? |
|
Definition
| Phystigmine or neostigmine. |
|
|
Term
| What happens with reversible inhibition of AChE? |
|
Definition
| prolongs duration and increases amplitude of EPP; agents slowly hydrolyzed and eventually lose effectiveness. |
|
|
Term
| What are some irreversible inhibitors of AChE? |
|
Definition
| Organophosphorous compounds. |
|
|
Term
| What happens during irreversible inhibition of AChE? |
|
Definition
| Excessive enhancement of cholinergenic transmission; produce death by flaccid paralysis of respiratoyr muscles due to depolarization blockade; made for very lethal nerve gases. |
|
|
Term
| Give an example of an organophosphorous compound. |
|
Definition
| Anatoxin (cyanobacteria). |
|
|
Term
| How is muscle classified histologically? |
|
Definition
Striated = cardiac or skeletal
Non-striated = smooth |
|
|
Term
| How is muscle classified in terms of control? |
|
Definition
Voluntary = skeletal
Involuntary = smooth and cardiac. |
|
|
Term
| How is muscle classified in terms of function? |
|
Definition
Skeletal (striated, voluntary): attaches to bones
Smooth (non-striated, involuntary): in hollow organs
Cardiac (striated, involuntary): walls of heart. |
|
|
Term
| Describe the gross anatomy of skeletal muscles. |
|
Definition
-composed of many bundles of elongated, multinucleated cells.
-muscle fibers separated into bundles called fasciculi by connective tissue sheath (perimysium).
-many fasciculi that make up a skeletal muscle are surrounded by a c.t. sheath (epimysium). |
|
|
Term
| Describe the microscopic anatomy of skeletal muscle. |
|
Definition
-membrane surrounding each muscle fiber is the sarcolemma
-each muscle fiber contains hundreds to thousands of myofibrils
-sarcoplasm lies between the myofibril and has mitochondria, several nuclei, and other organelles
-the ER of skeletal muscle is called SR and is very elaborate and highly specialized
-seen with light microscope, skeletal muscle fibers exhibit alternating light bands (I bands) and dark bands (A bands). |
|
|
Term
| What are I bands in skeletal muscle? |
|
Definition
| The light bands; regions of thin filaments that are not overlapped with thick filaments. |
|
|
Term
| What are A bands in skeletal muscle? |
|
Definition
| The dark band; the thick filaments. |
|
|
Term
| Describe the ultrastructure of skeletal muscle. |
|
Definition
-A dark line (Z line) bisects I band and divides myofibril into sarcomeres.
-thin filaments are attached to Z lines and interdigitate with the thick filaments
- in center of A band is a lighter region, the H band.
- The H band is bisected by a dark band of protein called the M line. |
|
|
Term
|
Definition
| A dark line that determines the border of the sarcomeres. |
|
|
Term
|
Definition
| The contractile unit of skeletal muscle and are composed of thick and thin filaments arranged in a precise manner. |
|
|
Term
|
Definition
| Has only thick filaments; located in the center of the A band; represents the distance between the ends of the thin filaments. |
|
|
Term
|
Definition
| A dark band of protein that links adjacent thick filaments to one another and maintains their alignment. |
|
|
Term
| What are thin filaments made of? |
|
Definition
| Actin, tropomyosin, and troponin. |
|
|
Term
|
Definition
| Molecule that consists of globular proteins (G actin) that polymerize into filamentous double stranded helix (F actin). |
|
|
Term
|
Definition
| A thin filamentous protein that lies along the actin molecule and prevents interaction of actin with myosin. |
|
|
Term
|
Definition
| A small molecule that acts as a regulatory protein. |
|
|
Term
| What do thick filaments consist of? |
|
Definition
|
|
Term
|
Definition
-Each myosin molecule contains two strands which at one end are twisted around each other to form a long tail and at the other form globular heads.
-the aggregation of the tail regions of many myosin molecules forms the thick filament.
-the head regions stick out away from the tails on flexible extensions of the myosin molecule and are called crossbridges. |
|
|
Term
| What other proteins are associated with the myofilaments? |
|
Definition
|
|
Term
|
Definition
| Stretches from Z line to end of each filament; regulates precise length of each thin filament. |
|
|
Term
|
Definition
| A spring-like protein connecting the Z line to the center of each thick filament. |
|
|
Term
| What are the functions of titin? |
|
Definition
-Maintains the organization and alignment of the thick filaments
-responsible for the passive elastic properties of muscle and allows muscle to recover after being stretched
-may also serve as a mechanoreceptor which participates in mechanical activity-dependent gene regulation and protein degradation. |
|
|
Term
| What do myosin crossbridge contain? |
|
Definition
|
|
Term
| What can myosin crossbridges act as? |
|
Definition
|
|
Term
| How is chemical energy transduced into mechanical energy in muscle? |
|
Definition
| The interaction of actin and myosin and the consequent splitting of ATP results in the transduction. |
|
|
Term
| What are the steps involved with the chemical to mechanical energy transduction? |
|
Definition
-Ca binds to troponin (leads to conformational change), which results in rotation of tropomyosin molecule which unveils myosin binding sites on the actin.
-Myosin, which in resting state is associated with ADP+Pi, has high affinity for actin and binds to it
-release of P from myosin begins power stroke and crossbridge rotates from 90 degree to 45 degree causing sarcomere to shorten; ADP is released at end of power stroke
-ADP-free myosin complex remains bound to actin until another ATP binds to myosin, which reduces affinity of myosin for actin
-actin and myosin separate and bound ATP is hydrolyzed
-energy from hydrolysis is utilized to re-cock the crossbridge from 45 degree to 90 degree and the crossbridge regains its high affinity for actin
-cycle continues until sarcoplasmic Ca levels return to normal |
|
|
Term
| What happens if muscle becomes depleted of ATP? |
|
Definition
| Rigor; myosin stays in attached state |
|
|
Term
| Name the types of contraction skeletal muscle can undergo. |
|
Definition
|
|
Term
| What is isometric contraction? |
|
Definition
| Contraction at constant length (no shortening). |
|
|
Term
| What is isotonic contraction? |
|
Definition
| Contraction at constant load (shortening). |
|
|
Term
| Do contractions have both isometric and isotonic components? |
|
Definition
|
|
Term
| What can make the isometric portion of contraction longer? |
|
Definition
|
|
Term
| Explain the force-length relationship. |
|
Definition
the force produced by a contraction depends on the length of the muscle and is proportional to the amount of overlap of thick and thin filaments in the sarcomeres
-the force needed to stretch a relaxed muscle primarily reflects the elastic properties of the c.t. in muscle and titin. |
|
|
Term
| What does the length-tension curve represent? |
|
Definition
| The relationship between muscle length and the amount of tension that a muscle can develop under isometric conditions; also describes the maximum shortening that a contracting muscle can undergo based on the load that it is bearing and the length at which the muscle began to shorten; has relationship with isotonic contraction because with it, muscle length is changing. |
|
|
Term
| What is the velocity of shortening determined by? |
|
Definition
| The load; heavier = slower |
|
|
Term
| What does maximum velocity correspond to? |
|
Definition
| Maximal cross-bridge cycling rate. |
|
|
Term
| What is the maximum velocity determined by? |
|
Definition
| ATPase activity of the myosin present. |
|
|
Term
| What is the sarcoplasmic reticulum? |
|
Definition
| An extensive membranous sac structure inside each muscle fiber. |
|
|
Term
| What does the SR consist of? |
|
Definition
| Almost entirely of Ca pumps that maintain a low intracellular Ca concentration by actively removing Ca from the sarcoplasm. |
|
|
Term
| What does the inside of SR contain? |
|
Definition
| A Ca binding protein called calsequestrin which reduces free Ca in the SR. |
|
|
Term
| What is excitation-contraction coupling? |
|
Definition
| The series of events whereby a depolarization leads to interactions between thick and thin filaments. |
|
|
Term
| What does E-C coupling involve? |
|
Definition
| Several steps which ultimately alter Ca levels. |
|
|
Term
| What are the steps of E-C coupling? |
|
Definition
-action potential initiated near NMJ travels along surface of muscle and into T-tubules which open to surface
- action potential in T tubules activates a voltage sensor, dihydropyridine (DHP) receptor, located in region of the triad
- DHP receptor undergoes a conformational change during which it interacts mechanically with a protein embedded in SR, the ryanodine receptor, as a result of this mechanical interaction, Ca channels in SR are opened
-Ca leaves SR and binds to tropinin
-this binding produces a conformational change and tropomyosin moves and reveals myosin binding site
-interaction occurs between actin and myosin and fiber contracts
-Ca pumps in SR are activated and Ca concentration is rapidly returned to resting levels producing relaxation. |
|
|
Term
| Explain pathological E-C coupling (Malignant Hyperthermia). |
|
Definition
-autosomal dominant genetic disorder
-affects 1 in 50,000 individuals
-triggered by inhalation anesthetics, particularly halothane, and succinylcholine
-prodced by an abnormality in ryanodine recepotr causing excessive Ca release from SR
-ATP consumption by Ca pumps of SR liberates heat producing the hyperthermia |
|
|
Term
| What are sources of ATP necessary for contraction and relaxation? |
|
Definition
| ATP pool, creatine phosphate, anaerobic metabolism (glycolitic), aerobic metabolism (oxidative phosphorylation). |
|
|
Term
|
Definition
| While ATP is source of energy for skeletal muscle contraction, ATP pool is small; only enough to support a few seconds o maximal contractile activity. |
|
|
Term
| What is creatine phosphate? |
|
Definition
| an immediate high energy source for replenishing ATP; converts ADP to ATP; provides only enough store for energy for less than a minute of maximal activity. |
|
|
Term
| Describe anaerobic metabilism's role with muscle contraction and relaxation. |
|
Definition
| Occurs when oxygen supply is inadequate; very rapid production of ATP from glucose or glycogen; inefficient because only 2 moles of ATP/mole glucose; final product of glucose breakdown is lactic acid. |
|
|
Term
| Describe aerobic metabolism. |
|
Definition
| occurs when oxygen is readily available; slow process for ATP production; utilizes fatty acids as primary energy source; efficient: 36 moles ATP/mole glucose; final metabolic byproducts are CO2 and H2O. |
|
|
Term
|
Definition
| The excess amount of O2 consumed after exercise has ceased; equal to energy consumed minus that supplied by oxidative metabolism. |
|
|
Term
| What is the purpose of the oxygen debt? |
|
Definition
| To replenish metabolic stores using aerobic metabolism; creatine phosphate and ATP levels returned to normal; lactic acid either turned back into glucose or glycogen or used to produce ATP. |
|
|
Term
| What types of skeletal muscle fibers are there based on contraction speed and metabolism? |
|
Definition
| Slow twitch and fast twitch. |
|
|
Term
| What are slow twitch fibers? |
|
Definition
| oxidative or Type I; smallest diameter muscle fibers; contain a myosin which splits ATP at relatively slow rate; highly developed capacity for aerobic metabolism (surrounded by many blood vessels, has myoglobin (red fibers), and contain many mitochondria); low glycogen content; fatigue resistant. |
|
|
Term
| What types of fast twitch fibers are there? |
|
Definition
|
|
Term
| Describe Type IIb fibers. |
|
Definition
| glycolyticc fibers on the opposite end of the spectrum from Type I; largest diameter; contain myosin which splits ATP at high rate; comparably few mitochondria; no myoglobin; high glycogen stores; fatigable (rely on anaerobic metabolism and quickly exhaust energy stores). |
|
|
Term
| Describe Type IIa fibers. |
|
Definition
| oxidative fibers; intermediate between Type I and Type IIb; muscle fibers between Type I and Type IIb; contain myosin which split ATP at high rate but not as high as Type IIb; higher number of mitochondria than Type IIb; contain myoglobin; abundant glycogen stores (more than Type I but less than Type IIb); fatigue resistant and greater capacity for aerobic metabolism than Type IIb. |
|
|
Term
| How are muscles classified as fast or slow twitch muscles? |
|
Definition
| Depending on the preponderance of one type of fiber or another. |
|
|
Term
| Classify Latissimus dorsi in terms of what type of muscle it is. |
|
Definition
| fast - glycolytic; individual fibers have large diameter; function is rapid movement; low endurance. |
|
|
Term
| Classify vastus lateralis in terms of what type of muscle it is. |
|
Definition
| fast - oxidative; moderate diameter fibers; function is moderately rapid movement; moderate endurance. |
|
|
Term
| Classify soleus in terms of what type of muscle it is. |
|
Definition
| slow - oxidative; small fiber diameter; function is postural; high endurance. |
|
|
Term
| Classify soleus in terms of what type of muscle it is. |
|
Definition
| slow - oxidative; small fiber diameter; function is postural; high endurance. |
|
|
Term
|
Definition
| A mechanical response to a single stimulation. |
|
|
Term
| What is the latent period? |
|
Definition
| 2-4 ms; the time between stimulus and initiation of contraction. |
|
|
Term
| What happens during the period of contraction? |
|
Definition
-actin and myosin interact
-muscle actively develops tension
-if tension is greater than load resistance have isotonic contraction
-if tension is less than load resistance have isometric contraction. |
|
|
Term
| What happens during the period of relaxation? |
|
Definition
| [Ca2+]i returns to normal; tension diminishes. |
|
|
Term
| What does twitch duration depend on? |
|
Definition
|
|
Term
| What kind of twitch duration do fast and slow twitch fibers have? |
|
Definition
Fast twitch: short twitch duration
Slow twitch: long twitch duration |
|
|
Term
| What are the factors influencing twitch duration? |
|
Definition
-different rates of ATP hydrolysis by myosin isoforms produce different rates of contraction
-differences in the rate of Ca uptake into SR: activity of Ca pumps in fast twitch fibers is greater than those in slow twitch fibers resulting in quicker Ca uptake and faster relaxation. |
|
|
Term
| What happens due to the duration of a muscle action potential being short compared to twitch duration? |
|
Definition
| Muscle can be activated again before it has fully relaxed. |
|
|
Term
|
Definition
| when a second action potential occurs during relaxation, the force it produces adds to that remaining from the first action potential. |
|
|
Term
|
Definition
| A sustained contraction produced by muscle action potentials occurring repeatedly and rapidly. |
|
|
Term
| What is the tetanic fusion frequency? |
|
Definition
| Teh frequency at which the action potentials will occur so rapidly that no relaxation occurs, producing a smooth or fused rise in tension to a plateau; tension is the maximum tension the muscle can produce. |
|
|
Term
| Compare the tension produced during a fused tetanus compared a single twitch. |
|
Definition
| Tension produced during plateau of fused tetanus is several times larger than a single twitch; ration varies from 3-8. |
|
|
Term
| What are factors influencing the development of tension? |
|
Definition
| Internal Ca concentration, series elastic elements and muscle length. |
|
|
Term
| Explain how internal Ca concentration plays a role in the development of tension. |
|
Definition
| -the reuptake of Ca begins as soon as the muscle is stimulated and the elevated Ca concentration is brief compared to development of tension; multiple stimuli are needed to maintain saturating levels of Ca. |
|
|
Term
| What are series elastic elements? |
|
Definition
| Structures in a muscle that are stretched when the muscle actively contracts; structures primarily responsible for series elasticity are the crossbridges but tendons also contribute. |
|
|
Term
| What is the effect of the series elastic elements on twitch tension? |
|
Definition
| After stimulation, Ca ion release, crossbridge formation and the consequent development of internal tension (active state) occur quickly; much of this tension must be used to stretch the series elastic elements before tension is transmitted to the load; less than full tension is transmitted to load. |
|
|
Term
| What is the effect of tetanus on series elastic elements? |
|
Definition
| during a tetanic contraction the repetitive stimuli maintain the internal tension so the series elastic elements remain stretched and more of the internal tension is applied to the load. |
|
|
Term
| How does muscle length influence the development of tension? |
|
Definition
| The amount of isometric tension produced by a muscle depends on its initial length; when the situation is such that the thin filaments overlap all the crossbridges, tension development is maximum. |
|
|
Term
|
Definition
| A motor neuron and all the muscle fibers it innervates. |
|
|
Term
| What happens in large motor units? |
|
Definition
| One neuron innervates many muscle fibers and movement is coarse. |
|
|
Term
| What happens in small motor units? |
|
Definition
| Only a few fibers are innervated by a single neuron and movement is more delicate. |
|
|
Term
| Are all muscle fibers in a motor unit the same? |
|
Definition
|
|
Term
| What do small motor units contain? |
|
Definition
| Slow, oxidative fibers and neurons with small diameter axons. |
|
|
Term
| What do large motor units contain? |
|
Definition
| Large diameter axons and fast, glycolytic fibers. |
|
|
Term
| Describe multiple motor unit (spatial) summation. |
|
Definition
| Simultaneous activity of motor units influence the degree of contraction; the more motor units that are simultaneously active, the greater the tension produced; small motor units are recruited first. |
|
|
Term
| Describe frequency (temporal) summation. |
|
Definition
| the amount of tension developed by an individual motor unit depends on its rate of stimulation; if rate of stimulation is high enough, twitches will sum and at high frequencies, tetanus of the fibers of the motor unit will occur. |
|
|
Term
| What are the general properties of smooth muscle? |
|
Definition
-muscles of hollow organs
-not attached to skeleton
-capable of sustained contractions with a minimum energy expenditure
-innervated by ANS (extrinsic innervation) and by neurons in plexuses within smooth muscle tissue (intrinsic innervation), especially in GI tract. |
|
|
Term
| Describe the histology of smooth muscle fibers. |
|
Definition
-uninucleate
-spindle shaped
-smaller than skeletal muscle fibers
-SR is not as elaborate as skeletal muscle
-no T-tubules but contain rows of caveloae |
|
|
Term
|
Definition
-increase surface-to-volume ratio
-often lie close to SR
-contain voltage-gated Ca channels as well as other proteins
-probably involved in many forms of signal transduction. |
|
|
Term
| What types of smooth muscle are there? |
|
Definition
| Single unit and multiunit. |
|
|
Term
| Describe single unit (visceral) smooth muscle. |
|
Definition
-most common type
-found in intestines, uterus, small arteries and veins
-cells connected by gap junctions, respond as a unit
-show spontaneous fluctuations in membrane potential that can lead to action potential production and contraction. |
|
|
Term
| What is multiunit smooth muscle. |
|
Definition
-less common
-located in iris and ciliary muscles
-few gap junctions; individual cells respond independently
-allows for finer control
-no spontaneous contractile activity and no action potentials. |
|
|
Term
| Describe contractile proteins. |
|
Definition
-contain myosin, actin, tropomyosin, but no troponin
-not organized into regularly ordered sarcomeres
-thin filament anchor to dense bodies
-each group of thin filaments surround a few thick ones
-more thin than thick filaments compared to skeletal muscle |
|
|
Term
| Explain the biochemistry of activation, contraction and relaxation of smooth muscle. |
|
Definition
-stimulation leads to increase in [Ca]i
-Ca binds to calmodulin
-Ca-calmodulin complex activates myosin light chain kinase (MLCK)
-MLCK phosphorylates light chains of myosin
-phosphorylated myosin interacts with actin, producing contraction
-Ca is actively pumped out of cell or into SR, causing a decrease in [Ca]i
-MLCK inactivates and phosphorylation of myosin stops
-MLC phosphatase dephosphorylates MLC
-smooth muscle relaxes
-contractile force produced by a smooth muscle is thus a balance between phosphorylation and dephosphorylation of myosin light chain. |
|
|
Term
| What happens if myosin is dephosphorylated while attached to actin? |
|
Definition
| It detaches slowly; Latch state. |
|
|
Term
| What happens if myosin is not attached to acin when dephosphorylated? |
|
Definition
| Myosin loses affinity for actin and does not continue cycling. |
|
|
Term
| What can the contractile force at any given Ca level be modulated by? |
|
Definition
| Altering the activity of the kinase and phosphatase. |
|
|
Term
| What does beta 2-receptor activation on vascular or bronchiolar smooth muscle do? |
|
Definition
-increase cAMP levels
-cAMP activates protein kinase A which phosphorylates MLCK
-phosphorylation reduces activity of MLCK resulting in less tension being produced. |
|
|
Term
| What does nitric oxide do? |
|
Definition
-increases intracellular cGMP levels
-cGMP activates protein kinase G which phosphorylates MLCK
-phosphorylation reduces activity of MLCK, resulting in less tension being produed. |
|
|
Term
| What does phospholipase C produce? |
|
Definition
| IP3 and diacylglycerol (DAG). |
|
|
Term
| What do IP3 and DAG do in smooth muscle? |
|
Definition
-IP3 induces Ca release from intracellular stores
-DAG activates protein kinase C which phosphorylates MLC phosphatase
-phosphorylation reduces activity of MLC phosphatase resulting in greater tension than would have otherwise been produced. |
|
|
Term
| Explain how Ca influx across the sarcolemma is regulated. |
|
Definition
-voltage-gated Ca channels
-receptor-regulated Ca channels
-store-operated Ca channels. |
|
|
Term
| Describe voltage-gated Ca channels. |
|
Definition
-abundant in smooth muscle cells
-Ca channels opened by dephosphorylation from either slow wave potentials or action potentials. |
|
|
Term
| Describe receptor-regulated Ca channels. |
|
Definition
-channels can be opened by neurotransmitters or hormones
-produce little or no depolarization. |
|
|
Term
| Describe store-operated Ca channels. |
|
Definition
-open when SR levels are low
-replenish SR Ca |
|
|
Term
| What regulates Ca efflux from SR? |
|
Definition
| Receptor-regulated efflux and Ca-induced Ca release from SR. |
|
|
Term
| Describe receptor-regulated efflux of Ca from SR. |
|
Definition
-binding of neurotransmitter or hormone to receptor causes formation of a second messenger (IP3) which causes release of Ca from SR
-doesn't involve membrane potential change. |
|
|
Term
| Describe Ca-induced Ca release from SR. |
|
Definition
Ca influx across sarcolemma release Ca from SR
-not as important as Ip3-induced release. |
|
|
Term
| How is extrusion of Ca from myoplasm regulated? |
|
Definition
| Sarcolemma pathway and SR pathway. |
|
|
Term
| What does the sarcolemma pathway of Ca extrusion consist of? |
|
Definition
| Ca pump and Na-Ca exchanger. |
|
|
Term
| What happens in SR pathway of Ca extrusion? |
|
Definition
-Ca pumps on SR pump Ca into SR
-SR contains Ca-binding proteins calreticulin in addition to calsequestrin. |
|
|
Term
| At what speed does the contraction relaxation cycle in smooth muscle go and why? |
|
Definition
-Slow.
-myosin has very slow attachment and detachment rates
-pumpin of Ca out of myoplasm is slow. |
|
|
Term
| What does crossbridge recycling in smooth muscle require? |
|
Definition
|
|
Term
| Are there any reserves (like creatine phosphate) available in smooth muscle? |
|
Definition
|
|
Term
| Where does most of the ATP needed for smooth muscle come from? |
|
Definition
|
|
Term
| How can ATP be produced in smooth muscles when O2 levels are low? |
|
Definition
|
|
Term
| How does the energy requirement for sustained contraction in smooth muscle compare to that in skeletal muscle? |
|
Definition
-much lower
-related to latch state. |
|
|
Term
| Explain the length-tension relationship of smooth muscle. |
|
Definition
| Smooth muscles can generate tension under greater stretch than skeletal muscles. |
|
|
Term
| Explain degree of shortening with smooth muscle. |
|
Definition
| Smooth muscles can undergo a greater degree of shortening than skeletal muscle. |
|
|
Term
| What is smooth muscle tone? |
|
Definition
| A sustained level of tension in a smooth muscle resulting from free Ca. |
|
|
Term
| What is the structure of the neuron-neuron synapse? |
|
Definition
-presynaptic ending
-prominent synaptic cleft
-postsynaptic neuron. |
|
|
Term
| Describe the presynaptic ending. |
|
Definition
-axon expands into a varicosity or a terminal bouton.
-has vesicles contianing neurotransmitter
-presence of electron dense region. |
|
|
Term
| Describe the postsynaptic neuron of neuron-neuron synapses. |
|
Definition
-electron dense region underlies that of presynaptc neuron but membrane not thrown into folds
-contains receptors for neurotransmitters. |
|
|
Term
| What kind of effect can the released transmitter produce on the postsynaptic cell? |
|
Definition
| Excitatory or inhibitory. |
|
|
Term
| Explain excitatory transmitter action. |
|
Definition
-conductance change drives membrane potential to a level that is less negative than threshold, results in increase in probability that postsynaptic cell wall produce an action potential
-produces a transient depolarization which is called the Excitatory Postsynaptic Potential (EPSP). |
|
|
Term
| Describe inhibitory transmitter action. |
|
Definition
-conductance change drives membrane potential to a level which is more negative than threshold and thus decreases probability that the postsynaptic cell will produce an action potential
-sometimes produces a transient hyperpolarization known as the Inhibitory Postsynaptic Potential (IPSP)
-important point is that inhibitory transmitters drive membrane potential to a level that is more negative than threshold. |
|
|
Term
| Describe the structure of a neuron. |
|
Definition
| Dendrites, cell body, axon. |
|
|
Term
|
Definition
-highly branched processes arising from cell body
-conduct messages toward cell body |
|
|
Term
| Describe cell body (soma). |
|
Definition
-contains nucleus and synthetic machinery.
-axon hillock- place where axon leaves soma. |
|
|
Term
|
Definition
-single process leaving soma at axon hillock region
-first part of axon is the initial segment
-trigger zone (axon hillock-initial segment region) is where action potentials originate
-carries information away from soma. |
|
|
Term
| Name ways to classify synapses. |
|
Definition
-axodendritic: synapse on dendrite of a neuron
-axosomatic: synapse on soma of neuron
-axoaxonic: synapse on the axon of a neuron. |
|
|
Term
| What are the general considerations of postsynaptic integration of synaptic inputs? |
|
Definition
-since AP are initiated only at trigger zone, AP activity of a neuron is governed by membrane potential at that site alone and that potential in turn is determined by the sum of all synaptic inputs impinging on the neuron at any given time
-because potential change produced by synaptic input is decrementally conducted to trigger zone, inputs closer to this site have greater influence. |
|
|
Term
| Describe spatial summation. |
|
Definition
-arrival of two or more separate inputs at the same time
-inputs either add to one another (e.g. two EPSPs) or subtract from one another (e.g. one EPSP and one IPSP). |
|
|
Term
| Describe temporal summation. |
|
Definition
| The build up of synaptic potentials during repetitive stimulation of single input because of the overlap in time of the postsynaptic responses. |
|
|
Term
|
Definition
-the increase in size of the postsynaptic response during reptitive stimulation of the presynaptic neuron
-lasts less than one second
-results from an increased number of transmitter quanta being released with each succeeding stimulus |
|
|
Term
| What happens at synapse when there is residual Ca left over from preceding action potentials. |
|
Definition
-release of one quantum requires simultaneous bindig of 4 Ca at release sites
-if another AP occurs before all Ca from preceding AP is taken up, new Ca adds to residual Ca causing greater release. |
|
|
Term
| Describe posttetanic potentiation. |
|
Definition
-enhancement of postsynaptic response after subjecting presynaptic neuron to high frequency stimulation for several seconds
-lasts up to several minutes after cessation of stimuli
-due to increased number of transmitter quanta being released per stimulus after the tetanic stimulation
-thought to be due to a saturation of Ca-buffering systems of neuron; excess Ca increases availability of vesicles for release. |
|
|
Term
| Describe long-term potentiation. |
|
Definition
-enhanced transmitter release after a strong tetanic stimulation
-lasts for days or longer
-involves both pre- and postsynaptic events
-serves as a cellular model for memory. |
|
|
Term
| Explain the pre- and postsynaptic events during long-term potentiation. |
|
Definition
-mediated through NMDA receptors on postsynaptic cell
-activation of NMDA receptor leads to production of a retrograde messenger (perhaps NO or CO)
-retrograde messenger diffuses from postsynaptic cell to presynaptic ending, causes an increase in transmitter output from presynapttic ending, probably by acitvating one of more second messenger systems. |
|
|
Term
|
Definition
-decrease in amount of transmitter released after a train of stimuli
-lasts a few sec to a few min depending on duration of stimulation
-occurs at synapses with a high quantal content and is due to depletion of vesicles available for release in presynaptic ending. |
|
|
Term
| Neurotransmitters are substances that: |
|
Definition
-are stored in vesicles at presynaptic ending
-released upon nerve activity
-diffuse to postsynaptic cell and combine with specific receptors
-produce a change in conductance in postsynaptic cell
-inactivation occurs by hydrolysis, uptake, or diffusion. |
|
|
Term
| Name some gaseous transmitters. |
|
Definition
|
|
Term
| How do gaseous transmitters behave? |
|
Definition
-nontraditionally
- not stored in vesicles but released when synthesized
-don't combine with surface receptors on postsynaptic cell but rather interact directly with second messenger systems (guanyl cyclase) inside
-inactivation presumably by diffusion away from target. |
|
|
Term
| Name some classic neurotransmitters. |
|
Definition
-acetylcholine
-biogenic amines
-amino acid transmitters |
|
|
Term
|
Definition
-primary transmitter of PNS
-participates in several pathways of CNS |
|
|
Term
| Degeneration of certain cholinergenic paths occurs in what disease? |
|
Definition
|
|
Term
| What are the biogenic amines? |
|
Definition
| Catecholamines, serotonin and histamine. |
|
|
Term
|
Definition
-synthesized from amino acid, tyrosine
-dopamine, norepinephrine, epinephrine |
|
|
Term
|
Definition
| Midbrain and diencephalon. |
|
|
Term
| Degeneration of DA pathways leads to what? |
|
Definition
|
|
Term
| What group of disorders are linked to DA systems? |
|
Definition
|
|
Term
|
Definition
| Primary transmitter of postganglionic sympathetics. |
|
|
Term
|
Definition
| Widespread NE projections from locus coeruleus in brainsteam to forebrain. |
|
|
Term
|
Definition
| Influence sleep, wakefullness, attention and feeding. |
|
|
Term
|
Definition
-established role as hormone in stress response
-recently identified a neurotransmitter in brain of unknown function. |
|
|
Term
|
Definition
5-hydroxytryptamine, 5-HT; synthesized from tryptophan
-implicated in onset of sleep, mood, emotional behavior, and certain psychotic disorders. |
|
|
Term
| Where is serotonin located? |
|
Definition
| Widespread projections from raphe nuclei in brainstem to brain and cerebellum. |
|
|
Term
| What is histamine synthesized from? |
|
Definition
|
|
Term
| Where is histamine present? |
|
Definition
| Mast ccells; in neurons of hypothalamus, which have widespread projections to almost all brain and spinal cord. |
|
|
Term
|
Definition
|
|
Term
| What are the amino acid transmitters? |
|
Definition
| Glycine, GABA, glutamate, and aspartate. |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Brainstem and spinal cord. |
|
|
Term
|
Definition
-Gamma-aminobutyric acid.
-important inhibitory transmitter of CNS. |
|
|
Term
| GABA deficit is implicated in what disorder? |
|
Definition
|
|
Term
|
Definition
-Polypeptides synthesized de novo in soma packaged in vesicles and transported via axoplasmic transport to axon terminals or sites of release
-some are synthesized as pre-propeptides and are cleaved to form appropriate final product in vesicles
-peptides function as neurotransmitters, neuromodulators and hormones. |
|
|
Term
| How do neuropeptides function as neurotransmitters? |
|
Definition
-released from presynaptic neuron and produce a conductance change in postsynaptic cell
-action terminated by diffusion and also peptidase |
|
|
Term
| How do neuropeptides function as neuromodulators? |
|
Definition
-don't necessarily produce a conductance change in target cell but do alter some aspect of cell function (e.g. excitability, amt of transmitter released, even products synthesized by cells)
-modulatory effects can be slow in onset and slow to dissipate
-all neuromodulators activate G-protein coupled receptors that stimulate an intracellular signal cascade (e.g. activation of adenylyl cyclase and elevation of cAMP). |
|
|
Term
| What are the classes of neuropeptides? |
|
Definition
Opioids, gut0brain and hypophysiotrophic
-many peptides can act as either neuromodulators or transmitters. |
|
|
Term
|
Definition
| Endorphin, enkephalin, dynorphin. |
|
|
Term
| What is endorphin derived from? |
|
Definition
|
|
Term
| What does endorphins bind to? |
|
Definition
| -preferentially to u receptors. |
|
|
Term
| What is enkephalin derived from? |
|
Definition
|
|
Term
| What does enkephalin bind to? |
|
Definition
|
|
Term
| What is dynorphin derived from? |
|
Definition
|
|
Term
| What does dynorphin bind to? |
|
Definition
|
|
Term
|
Definition
| Many neuropeptides and classical neurotransmitters are found in same nerve terminals. |
|
|
Term
| What are the gaseous transmitters/modulators. |
|
Definition
| Nitric oxide, carbon monoxide, hydrogen sulfide. |
|
|
Term
|
Definition
-first identified as endothelial-derived relaxing factor in blood vessels.
-synthesized from L-arginine by NO synthesis
-not stored in synaptic vesicles but instead diffuses from presynaptic terminal after synthesis
-doesn't bind to receptors on postsynaptic cell but rather diffuses into cell and directly interacts with second messenger systems (e.g. activation of guanylyl cyclase to increase cGMP). |
|
|
Term
| Explain carbon monoxide as a gaseous transmitter/modulator. |
|
Definition
-synthesized from heme by heme oxygenase
-readily diffuses through cell membranes thus released when synthesized
-one major action is activation of guanylyl cyclase. |
|
|
Term
| Describe directly gated ion channels. |
|
Definition
-also known as ligand-gated or ionotropic receptors.
-transmitter receptor is part of ion channel
-types include nicotinic ACh receptor, NMDA glutamate receptor, GABA receptor, glycine receptor. |
|
|
Term
| Explain how the transmitter receptor is a part of the ion channel. |
|
Definition
-single macromolecule forms both the recognition site and ion channel
-binding of neurotransmitter produces a conformational change in macromolecule which results in the opening of the channel. |
|
|
Term
| Describe the nicotinic ACh receptor. |
|
Definition
-binding of two ACh molecules initiates conformational change
-ion channel allows flux of Na into and K out of cell resulting in depolarization. |
|
|
Term
| Describe the NMDA glutamate receptor. |
|
Definition
-behavior is more complex than nicotinic ACh receptor
-cells which contain NMDA receptors usually have non-NMDA glutamate receptors as well; non-NMDA receptor activation depolarizes cell, which when increased, leads to NMDA channels being unplugged and current through channels increases
-Ca entry through NMDA channels results in activation of Ca-dependent 2nd messenger systems (Ca-calmodulin/kinase); too much Ca can result in cell death. |
|
|
Term
| How is the behavior of the NMDA glutamate receptor more complex than that of the nicotinic ACh receptor? |
|
Definition
-ion channel is plugged by Mg at resting potential and doesn't conduct well when activated by glutamate unless membrane is sufficiently depolarized to drive Mg out of cell
-once unplugged, the channel has high permeability to Ca as well as Na and K. |
|
|
Term
| Describe the GABA receptor. |
|
Definition
-receptor is responsible for most of inhibition in CNS
-GABA binding opens Cl selective channel
-in addition to a GABA binding site, the receptor has separate sites that bind other substances which modify GAVA receptor channel activity while having little effects by themselves
-GABA receptor can be modulated by second-messenger pathways. |
|
|
Term
| What substances can bind to GABA receptor and what do they do? |
|
Definition
-benzodiazepines (e.g. Valium): increases frequency of channel opening produced GABA and thus increase Cl current
-barbituates (e.g. Phenobarbital) increase duration of channel opneing produced by GABA and thus increase Cl current
-steroids (e.g. metabolites of testosterone): mimic effects of barbituates
-ethanol: increases GABA-induced Cl current. |
|
|
Term
| What are the second-messenger pathways that modulate the GABA receptor? |
|
Definition
-phosphorylation by either PKC or PKA reduces Cl current
-thus second-messenger pathways can also alter inhibitory activity in CNS. |
|
|
Term
| Describe the glycine receptor. |
|
Definition
-mediates most of the rest of inhibition in CNS not mediated by GABA
-glycine binding opens a Cl selective channel. |
|
|
Term
| Explain receptors that gate ion channels indirectly. |
|
Definition
-receptors linked to G-proteins and constitute the largest group of receptors
-receptor and ion channel are not part of same macromolecule but rather are distinct, separate entities linked together by a G protein |
|
|
Term
| How many pathways are there by which G-proteins modulate ion channels? |
|
Definition
|
|
Term
| Explain the membrane-delimited pathway. |
|
Definition
-G protein directly affects the ion channel
-binding of neurotransmitter to receptor activates G protein and the beta-gamma subunits of the G-protein diffuse through the membrane to interact with nearby channels
-example is M2 ACh receptor on heart which increases K permeability
-the properties include: relatively fast indirect pathway with latency of 30-100 ms; also relatively localized response because of limited diffusion of the G-protein within the membrane. |
|
|
Term
| What is the second pathway of receptors that gate ion channels indirectly? |
|
Definition
-G protein activates a second messenger system
-binding of neurotransmitter to receptor activates G-protein
-G-protein (usually alpha-subunit) activates enzyme which gives rise to 2nd messenger (e.g. Ca, cAMP, cGMP, IP3 and DAG, or arachidonic acid). |
|
|
Term
| What does the secondary messenger do in the second pathway? |
|
Definition
-directly modulates ion channel
0activates a kinase which phosphorylates a protein and this causes the channel to either open or close. |
|
|
Term
| What is an example of a receptor that uses the second pathway? |
|
Definition
| The beta 1 receptor activation by NE in heart leads to activation of adenylyl cyclase and increase in cAMP, which activates protein kinase A that phosphorylates L-type Ca channel leading to increase in Ca influx. |
|
|
Term
| What are the properties of the second pathway? |
|
Definition
-slow pathway with a latency of 100s to 1000s ms
-capable of wide spread effects of the production of soluble messengers which can diffuse throughout the cytoplasm
-capable of a great deal of amplification
-can generate very long-lasting changes in cell |
|
|
