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Updated: Jul 2, 2025

HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
Voltage tunes mGlu5 receptor function, impacting synaptic transmission
Marin Boutonnet1, Camille Carpena1, Nathalie Bouquier1
1IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.
Background And Purpose:
Voltage sensitivity is a common feature of many membrane proteins, including some G-protein coupled receptors (GPCRs). However, the functional consequences of voltage sensitivity in GPCRs are not well understood.
Experimental Approach:
In this study, we investigated the voltage sensitivity of the post-synaptic metabotropic glutamate receptor mGlu5 and its impact on synaptic transmission. Using biosensors and electrophysiological recordings in non-excitable HEK293T cells or neurons.
Key Results:
We found that mGlu5 receptor function is optimal at resting membrane potentials. We observed that membrane depolarization significantly reduced mGlu5 receptor activation, Gq-PLC/PKC stimulation, Ca2+ release and mGlu5 receptor-gated currents through transient receptor potential canonical, TRPC6, channels or glutamate ionotropic NMDA receptors. Notably, we report a previously unknown activity of the NMDA receptor at the resting potential of neurons, enabled by mGlu5.
Conclusions And Implications:
Our findings suggest that mGlu5 receptor activity is directly regulated by membrane voltage which may have a significant impact on synaptic processes and pathophysiological functions.
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