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Voltage tunes mGlu5 receptor function, impacting synaptic transmission
  • +6
  • julie perroy,
  • Marin Boutonnet,
  • Camille Carpena,
  • Nathalie Bouquier,
  • Yan Chastagnier,
  • Joan Font-Ingles,
  • Enora Moutin,
  • Ludovic Tricoire,
  • Jean Chemin
julie perroy
IGF

Corresponding Author:[email protected]

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Marin Boutonnet
IGF
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Camille Carpena
IGF
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Nathalie Bouquier
IGF
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Yan Chastagnier
IGF
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Joan Font-Ingles
IGF
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Enora Moutin
IGF
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Ludovic Tricoire
Sorbonne Universite
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Jean Chemin
IGF, CNRS, INSERM, University of Montpellier, Montpellier, France
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Abstract

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 TRPC6 channels or NMDA receptors. Notably, we report a previously unknown activity of the NMDA receptor at the resting potential of neurons, enabled by mGlu5. Conclusions & 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.
07 Sep 2023Submitted to British Journal of Pharmacology
08 Sep 2023Submission Checks Completed
08 Sep 2023Assigned to Editor
08 Sep 2023Review(s) Completed, Editorial Evaluation Pending
11 Sep 2023Reviewer(s) Assigned
06 Oct 2023Editorial Decision: Revise Minor