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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
PubMed
Summary
This summary is machine-generated.

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.

Keywords:
G‐protein coupled receptors (GPCR)biosensorsmetabotropic glutamate receptor (mGlu5)neuronal plasticitysignallingsynaptic transmissionvoltage sensitivity

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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.