Synaptic Transmission: Metabotropic

Question 1

What are the three G proteins associated with the effector pathways using G coupled receptors? What effector protein does it act on and in what way?

Answer 1

Gs: (+) adenylyl cyclase
Gq: phospholipase C
Gi: (-) adenylyl cylase

Question 2

Trace the following signal pathway from the effector protein adenylyl cyclase

Answer 2

adenylyl cylase (effector protein) –> cAMP (secondary messenger) –> Protein Kinase A (later effectors) –>phosphorylation (target action)

These can be all either increased or decreased depending on whether Gs or Gi

Question 3

Neurotransmitter for Gs

Answer 3

Epinephrine

Question 4

Neurotransmitter for Gi

Answer 4

Dopamine

Question 5

Neurotransmitter for Gq

Answer 5

Glutamate

Question 6

Trace the following signal pathway from the effector protein Phospholipase C (PLC)

Answer 6

PLC activates two secondary messengers:
Diacylglycerol –> Protein Kinase C (later effectors)
IP3 –> Ca2+ (later effectors

Both Protein Kinase C and Ca2+ increase protein phosphorylation and active calcium binding proteins

Question 7

Activated beta/gamma subunits of G protein (can/cannot) act directly on channel

Answer 7

They can act directly on channels

Question 8

4 important synaptic targets of GPCRs

Answer 8

1. Ligand gated channels
2. Cyclic nucleotide-gated channels
3. K+ channels in soma/dendrites
4. Modulate K+ and Ca2+ channels in presynaptic terminals

Question 9

What effects does GPCR signaling have on K+ and Ca2+ channels in presynaptic terminals?

Answer 9

Alter transmitter release (calcium channels trigger neurotransmitter release)

Question 10

Explain the effects of a K+ channel blockade

Answer 10

delayed repolarization (back to more negative) by potassium channel. Will give a broader action potential, cell stayed depolarized for longer period of time

Question 11

In basal condition, an action potential (is/is not) maintained during glutamate. Why or why not?

Answer 11

AP is not maintained due to activation of slow, non activating K+ channel, causes hyperpolarization (K+ leaves cell, becomes more negative inside), and inhibits firing

Question 12

With only a glutamate stimulus, AP firing is reduced over time due to ____

Answer 12

opening of the M-type K+ channels

Question 13

What allows the cell to maintain AP firing rate during glutamate? How?

Answer 13

ACh- by reducing hyperpolarization caused by K+ channels?

excitatory effect by DECREASING the channel conductance (inhibits the M-type K+ channel)

Question 14

Explain how ACh DECREASES the heart rate

Answer 14

Inhibitory effect of ACh muscarinic signaling. Activated a muscarinic receptor coupled to Gi, increases activity of K+ channel (channel open, K+ flow out, keep membrane potential close to negative K equilibrium)

Question 15

Inhibitory effect of GPCR signaling mediated by (increasing/decreasing) channel conductances

Answer 15

increasing channel conductances of K+ channel

Question 16

Backwards signaling across synapse (postsynaptic –> presynaptic)

Answer 16

Retrograde signaling

Question 17

Activation of this linked receptor in presynaptic axon inhibits presyaptic calcium influx

Answer 17

CB1

Question 18

Lipid molecules synthesized and released on-demand from plasma membrane. Chemically derived from?

Answer 18

Endocannabinoids- chemically derived from arachidonic acid

Question 19

Neurotransmitters are amino acids or aa-based, while endocannabinoids are?

Answer 19

Lipids (gases can also be neurotransmitters!)

Question 20

Transmitters are synthesized and stored in vesicles prior to release, meanwhile endocannabinoids are?

Answer 20

Synthesized on demand

Question 21

What causes normal transmitter release? How is this different for endocannabinoids?

Answer 21

can be triggered independently of Ca2+

Question 22

Indoleamine

Answer 22

serotonin

Question 23

Monoamine transmitter systems 1(3), 2(1)

Answer 23

Catecholamines- DA, NE, Epi

Indoleamine-Serotonin

Question 24

5 important features of monoamine transmitter systems

Answer 24

1. Relatively small # of neurons
2. Cell bodies in discrete brainstem nuclei
3. Widespread projections (single cell - 100,000 synapses)
4. Possible paracrine release of transmitter
5. Metabotropic (G protein coupled) receptors on post-synaptic

Question 25

Dopamine:

• brain stem nuclei
• receptors
• target for

Answer 25

• substantia nigra, ventral tegmental
• D1- like and D2-like receptors
• target for antipsychotics, parkinson’s, drug addiction

Question 26

Norepinephrine:

• brain stem nuclei
• receptors
• target for

Answer 26

• locus coeruleus
• alpha, beta adrenergic receptors
• target for antidepressants, anti-anxiety drugs

Question 27

Serotonin:

• brain stem nuclei
• receptors
• target for

Answer 27

• raphe nuclei
• 5-HT receptor subtypes
• target for antidepressants, OCD, panic disorder drugs

Question 28

In excitatory effect of ACh-muscarinic signaling, ACh activates ____ coupled to _____

Answer 28

muscarinic receptor coupled to Gq

Question 29

In excitatory effect of ACh-muscarinic signaling, Gq activation leads to what?

Answer 29

IP3-mediated increase in intracellular Ca2+

recall Gq–>phospholipase C –> IP3 —> Ca2+

Question 30

Role for PIP2 depletion in ACh-muscarinic signaling pathway

Answer 30

Phospholipid precursor that phospholipase C acts on. depletion of precursor changes function of other proteins in membrane

Question 31

In inhibitory effect of ACh-muscarinic signaling, ACh activates ____ coupled to _____

Answer 31

muscarinic reeptor coupled to Gi

Question 32

In inhibitory effect of ACh-muscarinic signaling, what acts directly on K+ channel to increase activity?

Answer 32

Beta gamma subunits. (Activate K channel, inhibitory effect, decrease heart rate)