Related Experiment Video
Updated: Jul 2, 2025
07:30
HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
7.3K
Voltage tunes mGlu5 receptor function, impacting synaptic transmission.
Marin Boutonnet1, Camille Carpena1, Nathalie Bouquier1
1IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.
British Journal of Pharmacology
|February 18, 2024
Summary
Metabotropic glutamate receptor 5 (mGlu5) activity is voltage-sensitive, functioning best at resting membrane potentials. Depolarization reduces mGlu5 activation, impacting synaptic transmission and neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Physiology
Background:
- Voltage sensitivity is a key characteristic of many membrane proteins, including G-protein coupled receptors (GPCRs).
- The functional implications of voltage sensitivity in GPCRs remain largely unexplored.
- Metabotropic glutamate receptor 5 (mGlu5) is a crucial postsynaptic receptor involved in synaptic plasticity.
Purpose of the Study:
- To investigate the voltage sensitivity of the mGlu5 receptor.
- To determine the impact of mGlu5 voltage sensitivity on synaptic transmission.
- To elucidate the role of membrane potential in regulating mGlu5 function.
Main Methods:
- Utilized biosensors and electrophysiological recordings.
- Studied mGlu5 receptor activity in HEK293T cells and primary neurons.
- Examined Gq-PLC/PKC signaling pathways and calcium (Ca2+) release.
Main Results:
- mGlu5 receptor activity is optimal at resting membrane potentials.
- Membrane depolarization significantly inhibits mGlu5 activation, Gq-PLC/PKC signaling, and Ca2+ release.
- Depolarization reduces mGlu5-mediated currents through TRPC6 and NMDA receptors.
- Discovered a novel role for mGlu5 in enabling NMDA receptor activity at resting neuronal potentials.
Conclusions:
- mGlu5 receptor activity is directly modulated by membrane voltage.
- Voltage-dependent regulation of mGlu5 may significantly influence synaptic processes.
- Altered mGlu5 voltage sensitivity could impact neurological disorders and pathophysiological functions.
Keywords:
G‐protein coupled receptors (GPCR)biosensorsmetabotropic glutamate receptor (mGlu5)neuronal plasticitysignallingsynaptic transmissionvoltage sensitivityMore Related Videos
07:16Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
13.6K
04:48A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
9.3K
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
01:19Ligand-gated Ion Channels
12.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.4K
01:26Neurochemical Transmission: Sites of Drug Action
2.3K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.3K
01:21G-protein Coupled Receptors
118.8K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
118.8K
01:26Chemical Synapses
8.8K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
8.8K
01:12GPCR Desensitization
6.0K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.0K