Term
| Do second messengers affect neural function through ion channels? |
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Definition
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Term
| What observation led to the discovery of second messengers? |
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Definition
| realizing that epinephrine (adrenaline) affects liver phosphorylase; doesn't cross the membrane though so how does it affect the phosphorylase? |
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Term
| Experiment for the discovery of second messengers (part 1): put liver cells ("liver homogenate") in a test tube, add epinephrine --> ? |
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Definition
| liver phosphorylase gets phosphorylated & activated |
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Term
| Experiment for the discovery of second messengers (part 2): start with liver homogenate in a test tube --> pour solution into a separate test tube but membranes are left behind --> add epinephrine --> ? |
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Definition
| nothing happens! LP isn't phosphorylated |
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Term
| Experiment for the discovery of second messengers (part 3): two test tubes (one has membrane pieces & cytoplasm...normal homogenate) --> add epinephrine --> separate out membrane & LP (centrifuging) --> put cytoplasm only (no LP) into test tube #2 (already containing normal homogenate) --> ? |
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Definition
| phosphorylated LP (activated) |
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Term
| What happens in the epinephrine causing phosphorylation of liver phosphorylase? |
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Definition
| epinephrine binds to metabotropic receptor to trigger process --> adenyl cyclase makes cAMP |
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Term
| 4 main ways metabotropic receptors affect neuronal activity |
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Definition
1. alterations of calcium channel function
2. alterations of potassium channel function
3. alterations in presynaptic active zone protein function
4. alterations in postsynaptic sensitivity to neurotransmitter |
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Term
| 2 main kinds of metabotropic receptors |
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Definition
1. presynaptic receptor (autocrine function)
2. postsynaptic receptor (paracrine function) |
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Term
| 3 ways metabotropic responses/effects are different from ionotropic |
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Definition
1. response takes longer than the ionotropic response
2. effects are not always as dramatic as ionotropic
3. the effects can last much longer than ionotropic! |
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Term
| When metabotropic receptors change the probability that calcium channels will open, is the neurotransmitter acting in an autocrine or paracrine manner? |
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Definition
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Term
| Experiment showing how metabotropic receptors modulate EPSPs (recording from B cell): stimulating sympathetic chain on B cell of sympathetic ganglion --> ? |
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Definition
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Term
| Experiment showing how metabotropic receptors modulate EPSPs (recording from B cell): stimulating spinal nerve root on C cell of sympathetic ganglion --> ? |
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Definition
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Term
| Experiment showing how metabotropic receptors modulate EPSPs (recording from B cell): stimulate sympathetic chain tetanically (on a train) --> ? |
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Definition
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Term
| Experiment showing how metabotropic receptors modulate EPSPs (recording from B cell): stimulate spinal nerve root on a train --> ? |
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Definition
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Term
| Experiment showing how metabotropic receptors modulate EPSPs (recording from B cell): stimulate sympathetic chain once after doing the train thing --> ? |
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Definition
| bigger EPSP than normally just stimulating it once |
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Term
| Do the many different metabotropic receptors funnel down into only a few or into a lot of g-protein complexes? |
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Definition
| only a couple of g-protein complexes |
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Term
| G-proteins interact with ______ to make the result in the cell of the transmitter interacting with the metabotropic receptor |
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Definition
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Term
| Are metabotropic receptors a single molecule or multiple? |
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Definition
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Term
| How many TMRs form a metabotropic receptor? |
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Definition
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Term
| Do metabotropic receptors have a diverse or conserved extracellular component (what binds to the ligands that activate it)? |
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Definition
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Term
| Do metabotropic receptors have a diverse or conserved intracellular component? |
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Definition
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Term
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Definition
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Term
| When the receptor is ______, g-proteins are associated with the receptor |
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Definition
| inactive (no neurotransmitter bound) |
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Term
| What is the big thing that is the main effect of switching g-proteins on or off? |
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Definition
| is GDP bound or is GTP bound? |
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Term
| 2 other names for metabotropic that use g-proteins |
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Definition
1. g-protein receptors
2. g-protein coupled receptors |
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Term
| Ligand binds to a GPCR, --> _____ binds to alpha subunit instead of ______ |
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Definition
| GTP binds to alpha subunit instead of GDP |
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Term
| Is the alpha GTP protein that binds to the effector protein membrane-bound or able to diffuse? |
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Definition
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Term
| Can beta gamma activate effector proteins? |
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Definition
| yes! (but this happens less often) |
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Term
| What does "RGS" stand for? |
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Definition
| "regulators of g-protein signaling" |
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Term
| The ______ subunit itself is a GTPase |
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Definition
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Term
| ______ phase: alpha, beta, & gamma subunits are bound with GDP |
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Definition
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Term
| When do g-proteins inactivate? |
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Definition
| when GTP gets cleaved down to GDP |
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Term
| Experiment with a cell that when glutamate binds to the receptor, g-proteins shut down calcium channels (calcium channels cannot open), recording whole-cell: cell with no glutamate in ECF --> ? |
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Definition
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Term
| Experiment with a cell that when glutamate binds to the receptor, g-proteins shut down calcium channels (calcium channels cannot open), recording whole-cell: cell with glutamate in ECF --> ? |
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Definition
| much less calcium current |
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Term
| Experiment with a cell that when glutamate binds to the receptor, g-proteins shut down calcium channels (calcium channels cannot open), recording whole-cell: no GTP in your whole-cell pipette, glutamate present --> ? |
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Definition
| normal calcium current (g-proteins cannot be activated without GTP!) |
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Term
| Experiment with a cell that when glutamate binds to the receptor, g-proteins shut down calcium channels (calcium channels cannot open), recording whole-cell: GTP-gamma-S in your whole-cell pipette, glutamate --> ? |
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Definition
| no calcium current (process cannot be reversed...can't inactivate) |
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Term
| Experiment with a cell that when glutamate binds to the receptor, g-proteins shut down calcium channels (calcium channels cannot open), recording whole-cell: GDP-beta-S in your whole-cell pipette, glutamate --> ? |
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Definition
| normal calcium current (stuck in inactive state!) |
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Term
| Different combinations of the different types of g-protein subunits --> ? |
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Definition
| nuanced/specific interactions |
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Term
| Experiment with a cell with a metabotropic ACh receptor (mAChR) & somatostatin receptor (also metabotropic) that reduce the activity of calcium channels: control response --> ? |
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Definition
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Term
| Experiment with a cell with a metabotropic ACh receptor (mAChR) & somatostatin receptor (also metabotropic) that reduce the activity of calcium channels: add ACh or somatostatin (SOM) --> ? |
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Definition
| reduction in calcium current |
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Term
| Experiment with a cell with a metabotropic ACh receptor (mAChR) & somatostatin receptor (also metabotropic) that reduce the activity of calcium channels: add ACh or SOM with the anti-sense for that g-protein --> ? |
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Definition
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Term
| What did the experiment with ACh & SOM metabotropic receptors that mess with calcium currents prove? |
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Definition
| realized that there were different types of each subunit |
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Term
| receptor-signaling compartmentalization |
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Definition
| a given transmitter receptor & its trimeric complex & its effector proteins are all right next to each other |
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Term
| Symptoms of whooping cough are mainly similar to ______ at first |
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Definition
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Term
| Where does whooping cough get its name? |
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Definition
| uncontrollable, violent coughing spells develop that include a "whooping" sound as patients breath in & gasp for air |
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Term
| Is whooping cough more serious for infants or adults? |
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Definition
| infants; can be life-threatening due to arrest of breathing |
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Term
| How is whooping cough spread? |
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Definition
| easily by coughing & sneezing |
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Term
| When can antibiotics be used to treat whooping cough? |
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Definition
| only if it is caught very early in the course of the infection |
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Term
| What bacteria causes whooping cough? |
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Definition
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Term
| Where is the Bordetella pertussis bacteria generally found? |
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Definition
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Term
| How does pertussis toxin affect g-proteins? |
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Definition
| ADP-ribosylates the Gi/o - alpha subunit, locking it into the GDP-bound inactive state |
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Term
| How does pertussis toxin affect adenylate cyclase? |
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Definition
| prevents inhibition of adenylate cyclase, leading to elevated levels of cAMP |
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Term
| When was the main cholera epidemic? |
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Definition
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Term
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Definition
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Term
| What bacteria releases the cholera toxin? |
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Definition
| Vibrio cholerae (in infected intestine) |
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Term
| CT is endocytosed into ______ cells |
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Definition
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Term
| How does the cholera toxin affect g-proteins? |
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Definition
| a fragment of the toxin acts as an enzyme that activates the Gs - alpha subunit & locks it in this GTP-bound form |
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Term
| How does cholera toxin affect adenylate cyclase? |
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Definition
| continuous stimulation of adenylate cyclase which produces cAMP |
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Term
| How does cholera toxin cause dehydration? |
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Definition
| leads to an efflux of chloride ions & water from intestinal cells leading to dehydration |
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Term
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Definition
| stimulate enkephalines which act through g proteins to inhibit cAMP formation, counteracting the effect of CT |
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Term
| basic scheme for metabotropic receptor signaling (4 steps) |
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Definition
| external signal (first messenger) --> receptor --> transducer/primary effector --> second messenger/secondary effector |
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Term
| How are metabotropic receptor signaling pathways normally named? |
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Definition
| for their primary effector |
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Term
| 4 major g-protein coupled signaling pathways |
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Definition
1. direct
2. cAMP system
3. phosphoinositol system
4. arachidonic acid system |
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Term
Which type of pathway is demonstrated by the following:
ACh --> mAChR --> Gk (transducer) & potassium channels (primary effector) --> open potassium channels (GIRK channels) |
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Definition
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): GIRK alone --> ? |
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Definition
| nominally 0% potassium channel activity |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): GIRK + beta-gamma dimer --> ? |
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Definition
| almost 100% potassium channel activity |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): GIRK + alpha-beta-gamma --> ? |
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Definition
| nominally 0% potassium channel activity |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): GIRK + alpha-beta-gamma heterotrimer + GTP-gamma-S --> ? |
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Definition
| almost 100% potassium channel activity |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): GIRK + alpha-GTP --> ? |
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Definition
| nominally 0% potassium channel activity |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (have the xenopus oocyte expressing potassium channels & mess around with g proteins & record potassium channel activity): result? |
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Definition
| it is the beta-gamma dimer that has an effect on the channels |
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (inside-out patch technique with a GIRK channel being the single channel): alpha-beta-gamma trimer + GTP-gamma-S --> ? |
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Definition
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (inside-out patch technique with a GIRK channel being the single channel): alpha-beta-gamma trimer --> ? |
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Definition
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (inside-out patch technique with a GIRK channel being the single channel): beta-gamma --> ? |
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Definition
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Term
| Experiment to determine which g protein dimer is involved in modulating GIRK channels (inside-out patch technique with a GIRK channel being the single channel): alpha-GTP --> ? |
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Definition
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Term
| basic scheme for metabotropic receptor signaling direct pathway (3 steps) |
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Definition
| external signal (first messenger) --> receptor --> transducer/primary effector |
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Term
| indirect pathway (starting with primary effector...three steps total) |
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Definition
| primary effector --> second messenger --> secondary effector |
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Term
| 3 indirect g-protein coupled signaling pathways |
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Definition
1. cAMP pathway
2. phosphoinositol pathway
3. arachidonic acid pathway |
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Term
| How are indirect g-protein coupled signaling pathways named? |
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Definition
| by the second messenger (made by the primary effector) |
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Term
| Is cAMP an example of a second messenger that can diffuse around the cell or is it necessarily membrane-bound? |
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Definition
| it can diffuse around the cell |
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Term
| Experiment testing a cAMP pathway that increases calcium current (doing whole-cell recording & calcium current): control --> ? |
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Definition
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Term
| Experiment testing a cAMP pathway that increases calcium current (doing whole-cell recording & calcium current): adding neurotransmitter X into the bath --> ? |
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Definition
| calcium current increased |
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Term
| Experiment testing a cAMP pathway that increases calcium current (doing whole-cell recording & calcium current): activate adenyl cyclase (no neurotransmitter involved yet) --> ? |
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Definition
| calcium current increased |
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Term
| Experiment testing a cAMP pathway that increases calcium current (doing whole-cell recording & calcium current): block PKA --> ? |
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Definition
| no change in current from control (no neurotransmitter to have activated PKA anyway, so you wouldn't see a change from the control) |
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Term
| How can you test the existence of a diffusible second messenger via whole-cell recording? |
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Definition
| if second messenger is diffusing, the channel current will eventually wash out & then the current will go away on your recordings |
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Term
| How do you test the existence of a diffusible second messenger doing a cell-attached recording? |
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Definition
1. add NE to the bath --> it cannot get to the specific receptor inside of your pipette (right next to your channel)
2. if it is diffusible second messenger, the receptors that can be bound to the NE will cause a second messenger that can diffuse over to the channel in the pipette despite its specific next-door receptor not being able to be accessed by the NE |
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Term
| 2 reasons for signal amplification of g protein-coupled signaling pathways |
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Definition
1. receptors can associate with multiple g proteins near them
2. each primary effector can generate many second messengers |
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Term
| 3 forms of signal regulation of g protein-coupled signaling pathways |
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Definition
1. receptor & g proteins uncouple
2. internalization of receptors
3. change in type of g protein coupled to a given receptor |
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Term
| main thing for signal termination of g protein-coupled signaling pathways |
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Definition
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