Synaptic Transmission: Metabotropic Flashcards
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?
Gs: (+) adenylyl cyclase
Gq: phospholipase C
Gi: (-) adenylyl cylase
Trace the following signal pathway from the effector protein adenylyl cyclase
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
Neurotransmitter for Gs
Epinephrine
Neurotransmitter for Gi
Dopamine
Neurotransmitter for Gq
Glutamate
Trace the following signal pathway from the effector protein Phospholipase C (PLC)
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
Activated beta/gamma subunits of G protein (can/cannot) act directly on channel
They can act directly on channels
4 important synaptic targets of GPCRs
- Ligand gated channels
- Cyclic nucleotide-gated channels
- K+ channels in soma/dendrites
- Modulate K+ and Ca2+ channels in presynaptic terminals
What effects does GPCR signaling have on K+ and Ca2+ channels in presynaptic terminals?
Alter transmitter release (calcium channels trigger neurotransmitter release)
Explain the effects of a K+ channel blockade
delayed repolarization (back to more negative) by potassium channel. Will give a broader action potential, cell stayed depolarized for longer period of time
In basal condition, an action potential (is/is not) maintained during glutamate. Why or why not?
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
With only a glutamate stimulus, AP firing is reduced over time due to ____
opening of the M-type K+ channels
What allows the cell to maintain AP firing rate during glutamate? How?
ACh- by reducing hyperpolarization caused by K+ channels?
excitatory effect by DECREASING the channel conductance (inhibits the M-type K+ channel)
Explain how ACh DECREASES the heart rate
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)
Inhibitory effect of GPCR signaling mediated by (increasing/decreasing) channel conductances
increasing channel conductances of K+ channel
Backwards signaling across synapse (postsynaptic –> presynaptic)
Retrograde signaling
Activation of this linked receptor in presynaptic axon inhibits presyaptic calcium influx
CB1
Lipid molecules synthesized and released on-demand from plasma membrane. Chemically derived from?
Endocannabinoids- chemically derived from arachidonic acid
Neurotransmitters are amino acids or aa-based, while endocannabinoids are?
Lipids (gases can also be neurotransmitters!)
Transmitters are synthesized and stored in vesicles prior to release, meanwhile endocannabinoids are?
Synthesized on demand
What causes normal transmitter release? How is this different for endocannabinoids?
can be triggered independently of Ca2+
Indoleamine
serotonin
Monoamine transmitter systems 1(3), 2(1)
Catecholamines- DA, NE, Epi
Indoleamine-Serotonin
5 important features of monoamine transmitter systems
- Relatively small # of neurons
- Cell bodies in discrete brainstem nuclei
- Widespread projections (single cell - 100,000 synapses)
- Possible paracrine release of transmitter
- Metabotropic (G protein coupled) receptors on post-synaptic
Dopamine:
- brain stem nuclei
- receptors
- target for
- substantia nigra, ventral tegmental
- D1- like and D2-like receptors
- target for antipsychotics, parkinson’s, drug addiction
Norepinephrine:
- brain stem nuclei
- receptors
- target for
- locus coeruleus
- alpha, beta adrenergic receptors
- target for antidepressants, anti-anxiety drugs
Serotonin:
- brain stem nuclei
- receptors
- target for
- raphe nuclei
- 5-HT receptor subtypes
- target for antidepressants, OCD, panic disorder drugs
In excitatory effect of ACh-muscarinic signaling, ACh activates ____ coupled to _____
muscarinic receptor coupled to Gq
In excitatory effect of ACh-muscarinic signaling, Gq activation leads to what?
IP3-mediated increase in intracellular Ca2+
recall Gq–>phospholipase C –> IP3 —> Ca2+
Role for PIP2 depletion in ACh-muscarinic signaling pathway
Phospholipid precursor that phospholipase C acts on. depletion of precursor changes function of other proteins in membrane
In inhibitory effect of ACh-muscarinic signaling, ACh activates ____ coupled to _____
muscarinic reeptor coupled to Gi
In inhibitory effect of ACh-muscarinic signaling, what acts directly on K+ channel to increase activity?
Beta gamma subunits. (Activate K channel, inhibitory effect, decrease heart rate)
