Term
| What are the 2 major divisions of the efferent portion of the nervous system? |
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Definition
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Term
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Definition
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Term
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Definition
| unconscious innervated structures of periphery |
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Term
| Where does control of the somatic nervous system originate? |
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Definition
| mortox cortex via corticospinal tracts |
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Term
| Where do all synapses of the somatic nervous system occur? |
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Definition
| within CNS (therefore motor neurons run from CNS to skeletal muscles uninterrupted) |
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Term
| Are somatic motor neurons usually myelinated or unmyelinated? |
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Definition
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Term
| That is the neurotransmitter for skeletal muscle? |
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Definition
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Term
| What happens to skeletal muscles if their innervation is lost? |
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Definition
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Term
| Where does control of the autonomic nervous system originate? |
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Definition
| hypothalamous, limbic system, & brain stem that integrate at the peripheral ganglia b/w CNS & neuroeffector junction. |
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Term
| What happens to smooth muscles & glands in the absence of functional autonomic innervation? |
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Definition
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Term
| What are the 2 major portions of the autonomic nervous system? |
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Definition
Parasympathetic
Sympathetic |
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Term
| What is the PS comprised of? |
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Definition
| autonomic output of the cranial nerves & sacral portion of the SC |
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Term
| What is the neurotransmitter at all ganglionic & neuroeffector junctions of the PS? |
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Definition
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Term
| What is the SS comprised of? |
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Definition
| autonomic output of the thoracic & lumbar portions of the SC |
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Term
| When is Ach the neurotransmitter in SS? |
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Definition
| sympathetic ganglia, adrenal medulla, & few sympathetic neuroeffector junctions |
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Term
| What is the neurotransmitter dominant at the neuroeffector junctions of the SS? |
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Definition
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Term
Which of the autonomic system is "rest & digest"?
"fight or flight"? |
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Definition
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Term
| What could be regarded at the 3rd component of the ANS? |
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Definition
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Term
| Where is the enteric nervous system found? |
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Definition
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Term
| What modulates the intrinsic activity of the enteric nervous system? |
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Definition
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Term
| What outputs does the enteric nervous system have? |
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Definition
| cholinergic & NANC (non-adrenergic, noncholinergic) |
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Term
| What are the primary neurotransmitters of the enteric nervous system? |
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Definition
| peptides, purines, & other substances (NO) |
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Term
| What do peptides, purines, & other substances function as in cholinergic & adrenergic neurons? |
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Definition
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Term
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Definition
| any neuron in CNS or periphery that liberates Ach as it's transmitter |
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Term
| What is the primary signal for all neurons leaving the CNS? |
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Definition
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Term
| What receptor type do all Ach originating from CNS synapse on initially? |
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Definition
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Term
| When are muscarinic Ach receptors used? |
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Definition
| In SS sweat glands & PS AFTER they initially synapse on a nictotinic Ach receptor |
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Term
| Where is Ach synthesized? |
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Definition
| cytoplasm of cholinergic nerve terminals |
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Term
| What 2 substrates are used to form Ach? |
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Definition
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Term
| What enzyme catalyzes Ach synthesis? |
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Definition
| ChAT (choline acetyltransferase) |
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Term
| Where is ChAT synthesized? |
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Definition
| cell body of neuron & transported down axon |
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Term
| Why is the rate of Ach synthesis dependent on choline? |
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Definition
| aceytl CoA is produced via mitochondria in the nerve, choline is selectively pumped into the nerve. |
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Term
| What amine type is choline? |
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Definition
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Term
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Definition
| contents of a single vesicle of Ach |
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Term
| How does Ach end up in vesicles? |
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Definition
| packaged into vesicles in nerve terminal |
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Term
| What singals Ach vesicles to fuse with the membrane & be relesed to synapse? |
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Definition
| Terminal becomes excited by action potential => Ca2+ channels activated => Ca2+ influx |
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Term
| What can effect Ca2+-dependent Ach release? |
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Definition
| Any Ca2+ antagonist interfering with permeability of Ca2+ |
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Term
def
MEPP (mini end plate potential) |
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Definition
| Sm. transient depolarization of the motor end plate via spontaneous release of individual quanta NOT cauing an AP |
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Term
| Why are graded responses in Ach release needed in the heart, visceral organs, or glandular tissue? |
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Definition
1) Single AP doesn't provide maximal response
2) released Ach must diffuse more widely due to less organized neuromuscular junction |
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Term
| What is the postsynaptic cholinoreceptor for Ach? |
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Definition
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Term
| What enzyme degrades Ach? |
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Definition
| AChE (acetylcholinesterase) |
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Term
| What does the cholinergic mediated response depend on? |
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Definition
| Ach binding postsynaptic AchR |
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Term
| How do presynaptic receptors play a role in neurotransmission? |
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Definition
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Term
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Definition
| By effects of agonists (muscarine & nicotine) & effects of antagonists (atropine & s-tubocurarine) |
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Term
| What does the flexibility of Ach allow it to bind to? |
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Definition
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Term
| What does the flexibility of Ach allow it to bind to? |
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Definition
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Term
| What on all cholinoreceptors allows the + charged Ach to orient over the binding site? |
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Definition
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Term
| Why do Ach analogs tend to have preference over receptor type/subtype? |
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Definition
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Term
What stimulates muscarinic receptors (mAch)?
What blocks mAch? |
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Definition
Stimulates: Ach
Blocks: atropine |
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Term
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Definition
| alkaloid isolated from Amanita muscaria mushroom |
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Term
| What 5 locations does muscarine mimic Ach? |
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Definition
1) visceral smooth muscle GI, LUT, uterus, bronchi
2) heart/vasculature
3) secondary glands
4) CNS
5) autonomic ganglia (primary cholinoreceptor is nicotinic, tho) |
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Term
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Definition
| an alkaloid from the leaves of atopine belladonna |
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Term
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Definition
| all cholinoreceptors that are activated by muscarine & blocked by atropine. They traverse the membrane 7 times. |
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Term
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Definition
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Term
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Definition
| mAchR predominant in the heart |
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Term
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Definition
| mAchR predominant in secretory signals |
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Term
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Definition
| a liquid alkalois isolated from tobacco |
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Term
| What are the 4 cholinoreceptor sites where nicotine acts as an agonist? |
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Definition
1) Neuromuscular junction of somatic muscles
2) all autonomic ganglia on dendrites of post-ganglionic neurons
3) CNS
4) adrenal medulla |
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Term
| What happens when nictotine binds to AchR in low concentrations? |
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Definition
| stimulation followed by recovery |
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Term
| What happens when nictotine binds to AchR in high concentrations? |
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Definition
| stimulation followed by depression |
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Term
| What causes the depression seen in high nicotine concentrations after stimulation? |
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Definition
| sustained depolarization of receptor membrane due to ionic channels being kept open |
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Term
def
depolarization blockade |
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Definition
| effect of large nicotine cocentrations |
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Term
| What blocks the stimulatory action of nicotine? |
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Definition
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Term
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Definition
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Term
def
nicotinic AchR (nAchR) |
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Definition
cholinoreceptor stimulated by nicotine & blocked by d-turbocurarine
They are pentameric complexes that span the membrane several times. |
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Term
| What are mAchR coupled with to transduce signals & cellular responses? |
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Definition
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Term
| Which mAchR's are coupled through Gi? |
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Definition
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Term
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Definition
| increased K+ conductance => inhibitory to cellular activity
decreased cAMP => decreased AC |
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Term
| What are the 3 subunits of the G protein? |
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Definition
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Term
| What subunit of G protein is responsible for it's function? |
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Definition
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Term
| When does the G protein α subunits dissociate from the βγ subunits? |
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Definition
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Term
| When does G protein α subunit rejoin βγ subunits? |
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Definition
| After GTP hydolyzed to GDP by α subunit |
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Term
| Which mAchR's are coupled through Gq? |
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Definition
| Odd mAchR's (M1, M3, & M5) |
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Term
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Definition
| increase cytosolic calcium => stimulatory to cellular activity
(via phospolipase C activation => conversion of PIP2 to PIPG3 & DAG => intracellular stroage release of calcium) |
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Term
| What is formed when nictotinic receptors are bound to agonists? |
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Definition
| conformational change to a poor allowing Na+, K+, & Ca2+ permeability |
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Term
| Why is it possible to selectively block nitotinic receptors either at autonomic ganglia or neuromuscular junction? |
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Definition
| Though both nAchR's, there are subtle differences at the binding sites. |
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Term
| Why does synaptically released Ach have a very short half life? |
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Definition
| presence of cholinesterases |
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Term
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Definition
| hydrolyze ester linkage of Ach => choline & acetic acid |
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Term
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Definition
| cholinergic/effector cell membranes & RBC membranes |
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Term
| Why is AchE so rapid to degrade Ach? |
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Definition
| to limit duration of action of Ach at cholinergic junctions |
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Term
| Where are pseudocholinesterases found? |
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Definition
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Term
Function
pseudocholinesterases |
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Definition
| less selective hydrolyzation of esters |
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Term
| Why is Ach relatively ineffective as a drug? |
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Definition
| it's rapidly metabolized in plasma |
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Term
| What are the 2 primary sites that Ach interacts contained on AchE? |
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Definition
| anionic site & esteratic site |
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Term
| What attracts the Ach to AchE? |
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Definition
| the (-) charge of anionic site draws in the (+) charge of quaternary amine of Ach => orients Ach over esteratic site for ester link hydrolysis |
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Term
| What releases choline from Ach in AchE? |
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Definition
| enzyme transfer of acetyl group to serine residue |
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Term
| What causes acetic acid release from AchE after choline leaves? |
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Definition
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Term
| What happens to the free choline after Ach breakdown by AchE? |
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Definition
| pumped back into nerve terminal or diffused away |
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Term
| What are the common pre-synaptic AchR's? |
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Definition
|
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Term
|
Definition
| regulate evoked release of Ach (feedback inhibition) i.e. prevent excessive Ach release |
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Term
| Why can low doses of atropine produce a paradoxical bradycardia? |
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Definition
| presynaptic AchR's = mAchR's. mAchR's are blocked by atropine => less feedback inhibition of presynaptic Ach release |
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Term
Function
presynaptic nAchR at neuromuscular junction |
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Definition
| stimulatory for Ach release to maintain Ach release during periods of intense neuromuscular transmission |
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Term
Pharmacologic sites of action at cholinergic synapses
[image]
|
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Definition
| 1) Ach synthesis
2) Ach storage
3) Prevent nerve terminal activation
4) Interfer with Ca2+ influx to nerve terminal via Ca2+ antagonists (NOT Ca2+ channel blockers)
5) Exocytosis modification
6) AchR Action
7) AchE inhibition |
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Term
| How do drugs affect Ach synthesis? |
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Definition
| Inhibit the rate-limiting step (choline uptake to nerve terminal) |
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Term
| How do drugs affect Ach storage? |
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Definition
| Prevent Ach packaging into secretory vesicle |
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Term
|
Definition
| blocks rate-limiting step of Ach synthesis |
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Term
|
Definition
| Inhibit Ach vesicle formation |
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|
Term
| What can prevent activation of nerve terminal? |
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Definition
|
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Term
| What interfers with Ca2+ influx to nerve terminal? |
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Definition
| hypermagnesia (or other Ca2+ antagonists, NOT Ca2+ channel blockers) |
|
|
Term
| What inhibits Ach exocytosis? |
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Definition
|
|
Term
| What activated Ach exocytosis? |
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Definition
|
|
Term
|
Definition
| agents that occupy cholinesterase Ach binding sites |
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Term
def
reversible indirect Ach agonist |
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Definition
indirect Ach agonist agents metabolized or removed from binding site within minutes-hours
or they are simple, competitive inhibitors of Ach binding |
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Term
def
irreversible indirect Ach agonist |
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Definition
| indirect Ach agonist agents that have stable covalent binding to esterases & remain on the AchE receptor for hours-days |
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Term
| What is an example of an irreversible indirect Ach agonist? |
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Definition
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Term
| Patient has primary axillary hyperhydrosis (excessive sweating) that has not responded to topical treatment. What agent may be appropriate for this patient. |
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Definition
|
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Term
| When can botox be used pharmacologically? |
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Definition
| strabismus, torticollis, wrinkles, possibly migranes |
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