Neurotransmitter Receptors II: Metabotropic Focus

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Questions and Answers

What role does the second intracellular loop (i2) play in mGluR functions?

It enhances AMPAR activation.

It functions independently of ion influx.

It facilitates fast synaptic transmission.

It is essential for G-protein coupling. (correct)

Which type of mGluR primarily activates Gq signaling?

Class II mGluRs

Class III mGluRs

All metabotropic receptors

Class I mGluRs (correct)

What is the result of mGluR1 activation?

Induces fast EPSC predominantly.

Leads to AMPAR-independent synaptic transmission.

Causes a slow EPSC through TRPC3 activation. (correct)

Inhibits the influx of Ca2+.

What primarily mediates calcium influx during mGluR1 signaling?

TRPC3 activation Signup and view all the answers

Which of the following statements about fast and slow EPSCs is true?

Only slow EPSCs rely on TRPC3. Signup and view all the answers

What potential mechanism does the C-terminal domain of mGluRs contribute to?

G-protein interaction facilitation Signup and view all the answers

Which ion's levels increase as a result of TRPC3 activation during mGluR1 signaling?

Ca2+ Signup and view all the answers

In the context of mGluRs, what does EPSC stand for?

Excitatory Post Synaptic Current Signup and view all the answers

What ion channels are activated by the increase in DAG levels resulting from mGluR1-mediated voltage-gated calcium channels?

TRPC3 channels Signup and view all the answers

What is the primary action of Class II mGluRs on calcium influx?

Attenuates Ca2+ influx Signup and view all the answers

Where are Class III mGluRs predominantly located?

On presynaptic terminals of glutamatergic and GABAergic neurons Signup and view all the answers

What type of proteins do Class II mGluRs couple to?

Gi/o proteins Signup and view all the answers

What is the primary effect of the activation of mGluR1 on dendritic signaling?

Slow depolarization of the neuron Signup and view all the answers

What is the primary role of mGluRs in the brain's neurotransmission?

Modulating both excitatory and inhibitory neurotransmission Signup and view all the answers

Which of the following is NOT a characteristic of Class II mGluRs?

Increase neurotransmitter release Signup and view all the answers

What ionic activities are associated with TRPC3 channel activation?

Simultaneous Na+ and Ca2+ conductance Signup and view all the answers

Which muscles contain the highest expression of M1 muscarinic ACh receptors?

Cerebral cortex Signup and view all the answers

What is the primary role of presynaptic M1Rs in neurotransmission?

Facilitate ACh release Signup and view all the answers

Which of the following is NOT a major type of muscarinic ACh receptor mentioned?

M6 Signup and view all the answers

What mechanism is primarily activated by postsynaptic M1Rs?

Slow postsynaptic depolarization Signup and view all the answers

Which G protein is associated with the activation of presynaptic M1Rs?

Gq Signup and view all the answers

How do M2 and M4 muscarinic receptors primarily function within the brain?

Presynaptic inhibitory receptors Signup and view all the answers

What is the outcome of activating postsynaptic M1Rs in terms of neuronal activity?

Increased neuronal excitability Signup and view all the answers

Which of the following describes the expression pattern of M3 and M5 muscarinic receptors?

Significantly lower levels than M1 Signup and view all the answers

What is the primary mechanism by which agonist binding affects GPCR conformation?

It stabilizes the active conformation. Signup and view all the answers

What characterizes negative antagonism in GPCR signaling?

It impedes the transition to the active state. Signup and view all the answers

Which type of GPCR is primarily associated with muscarinic acetylcholine receptors?

mAChRs Signup and view all the answers

What role does the i3 region play in GPCR activation?

It is essential for G-protein coupling and activation. Signup and view all the answers

What effect does antagonist binding have on GPCRs?

It prevents further transition to either state. Signup and view all the answers

Which of the following describes the function of mGluRs?

They are metabotropic glutamate receptors. Signup and view all the answers

What does GPCR desensitization refer to?

It reduces receptor signaling efficacy. Signup and view all the answers

Which of the following is NOT a type of GPCR mentioned?

ADH receptors Signup and view all the answers

How do GPCRs mainly transmit signals?

By activating downstream effector proteins. Signup and view all the answers

What is a key feature of G protein coupling?

It is highly selective and efficient. Signup and view all the answers

What is the role of GABA B2 in relation to GABA B1?

It stabilizes the agonist-bound conformation of GABA B1. Signup and view all the answers

What happens to cAMP levels when Gi/o proteins are activated?

cAMP levels decrease. Signup and view all the answers

Which of the following mechanisms is primarily responsible for preventing neurotransmitter release at presynaptic sites?

Inhibition of SNARE complex proteins. Signup and view all the answers

How does GABA B2 contribute to G protein coupling?

By stabilizing GABA B1's conformation. Signup and view all the answers

What is the primary effect of Gβγ-mediated inhibition of voltage-dependent calcium channels?

It reduces intracellular calcium influx. Signup and view all the answers

What would be the consequence of inhibiting voltage-dependent calcium channels in presynaptic neurons?

Decreased neurotransmitter release. Signup and view all the answers

What is the overall effect of GABAB receptor activation on synaptic transmission?

Inhibits neurotransmitter release. Signup and view all the answers

Which G protein subunit is directly involved in the inhibition of adenylyl cyclase?

Gα subunits. Signup and view all the answers

What initiates endocytosis of GPCRs?

Conformational change in b-arrestin Signup and view all the answers

After endocytosis, what is the primary function of protein phosphatases on GPCRs?

To dephosphorylate the GPCRs Signup and view all the answers

What role does AP2 play in the endocytosis of GPCRs?

It assists in the formation of clathrin-coated pits Signup and view all the answers

What occurs to GPCRs in the sorting endosome?

GPCRs are targeted either for recycling or degradation Signup and view all the answers

Which type of endocytic vesicle does not recycle GPCRs?

Lysosomal vesicles Signup and view all the answers

Which event directly follows the binding of GPCRs to their ligands?

Conformational change in the GPCR Signup and view all the answers

What is the immediate consequence of GPCR desensitization?

Decrease in receptor sensitivity to ligands Signup and view all the answers

The interaction of which protein with GPCRs promotes endocytosis?

b-arrestin Signup and view all the answers

Study Notes

Neurotransmitter Receptors II: Metabotropic Receptors

Metabotropic receptors are G protein-coupled receptors (GPCRs)
They are involved in neurotransmission
They have seven transmembrane domains
Activation of these receptors is initiated by neurotransmitters binding
They mediate slower, longer-lasting responses in comparison to ionotropic receptors

The Life Cycle of Neurotransmission

I. Synthesis (1-2): Neurotransmitters are created in the neuron.
II. Storage (3): Neurotransmitters are stored in vesicles within the neuron.
III. Release: Neurotransmitters are released from the presynaptic neuron into the synaptic cleft.
IV. Receptor Binding (4-5): The neurotransmitters bind to receptors on the postsynaptic neuron.
V. Transmitter Inactivation (6-9): Excess neurotransmitters are either broken down or reabsorbed by the presynaptic neuron.

Ionotropic vs. Metabotropic Actions

GPCR General Structure: GPCRs are single polypeptide chains with seven membrane-spanning helical segments wrapped through the membrane.
GPCR Activation and Action: Includes binding to G proteins.
Effector Mechanisms: Presynaptic and Postsynaptic: Specify the mechanisms of action for pre- and post-synaptic actions.
GPCR Types and Specific Mechanisms: Includes mGluRs, mAChRs, GABA_BRs, Dopamine and Serotonin receptors.
GPCR Desensitization: Describes how receptors lose sensitivity and function over time.

Common G protein Effector Targets

cAMP system: Norepinephrine and ACh activate the cAMP system, which leads to protein activation.
Phosphoinositol system: Involves ACh and norepinephrine triggering cascades that result in various downstream effects.

Ligand-induced GPCR Conformational Changes Activate G proteins

Agonist binding creates a conformational shift in the GPCR, inducing an active state.
The shift facilitates an interaction with G proteins.
Conformational changes enable activation of particular downstream pathways.

General Mechanisms of GPCR Modulation of Synaptic Transmission

Presynaptic GPCRs: Neurotransmitter Release
- G_α: Modifies neurotransmitter release via PKA and PKC targets. This occurs due to modulation of proteins involved in vesicle recruitment, docking, and fusion. In turn, this can either inhibit or facilitate synaptic transmission.
- G_βγ: Inhibits voltage-dependent calcium channels and regulates GIRK channels.
Presynaptic GPCRs: Neurotransmitter Release
- G_βγ: Inhibits voltage-dependent calcium channels and regulates GIRK channels.
- Inhibition of SNARE complex.
- Regulation of G protein-gated inward-rectifier K+ channel (GIRK) channels.

Postsynaptic GPCRs: Excitability

PKA-mediated closure of K+ channels.
Changes in transcription and chromatin structure, e.g., PKA activation of CREB.

Dopamine Metabotropic Receptors

D1-like receptors: Stimulate cAMP production and activate further downstream pathways.
D2-like receptors: Inhibit cAMP production and activate different signaling cascades.

Serotonin Metabotropic Receptors

Diverse families of serotonin receptors, each leading to specific effects based on activation pathways.
Function predominantly as postsynaptic receptors.

GPCR Desensitization

Heterologous desensitization: Desensitization of receptors occurs without ligand binding.
Activation by GPCR kinases (GRKs) and interactions with arrestin disengage the G-protein.
Homologous desensitization: Desensitization requiring ligand binding.
Phosphorylation by GRKs triggers ẞ-arrestin binding, promoting GPCR internalization.

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Description

This quiz delves into the specifics of metabotropic receptors, examining their role in neurotransmission and comparison to ionotropic receptors. Learn about the life cycle of neurotransmission, from synthesis to inactivation, while gaining insights into the structure and function of G protein-coupled receptors.