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Article Dans Une Revue British Journal of Pharmacology Année : 2024

Voltage tunes mGlu 5 receptor function, impacting synaptic transmission

Résumé

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 mGlu 5 and its impact on synaptic transmission. Using biosensors and electrophysiological recordings in non‐excitable HEK293T cells or neurons. Key Results: We found that mGlu 5 receptor function is optimal at resting membrane potentials. We observed that membrane depolarization significantly reduced mGlu 5 receptor activation, Gq‐PLC/PKC stimulation, Ca 2+ release and mGlu 5 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 mGlu 5 . Conclusions and Implications: Our findings suggest that mGlu 5 receptor activity is directly regulated by membrane voltage which may have a significant impact on synaptic processes and pathophysiological functions.
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Dates et versions

hal-04477169 , version 1 (26-02-2024)

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Citer

Marin Boutonnet, Camille Carpena, Nathalie Bouquier, Yan Chastagnier, Joan Font-Ingles, et al.. Voltage tunes mGlu 5 receptor function, impacting synaptic transmission. British Journal of Pharmacology, In press, 181 (12), pp.1793-1811. ⟨10.1111/bph.16317⟩. ⟨hal-04477169⟩
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