G-protein-mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer

Yin Shen, Melissa Ann F. Rampino, Reed C. Carroll, Scott Nawy

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

ON bipolar cells are critical for the function of the ON pathway in the visual system. They express a metabotropic glutamate receptor (mGluR6) that, when activated, couples to the Go class of G protein. The channel that is primarily responsible for the synaptic response has been recently identified as the transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1 is negatively coupled to the mGluR6/Go cascade such that activation of the cascade results in closure of the channel. Light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein activation in the dark is a critical step in the process of ON bipolar cell signal transduction, but the precise pathway linking these two events is not understood. To address this question, we measured TRPM1 activity in retinal bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the Gβγ subunit dimer, but not Gαo, closed TRPM1 channels in every cell type that we tested. In addition, activation of an endogenous G-protein-coupled receptor pathway in HEK293 cells that releases Gβγ without activating Go protein also closed TRPM1 channels. These results suggest a model in which the Gβγ dimer that is released as a result of the dissociation from Gαo upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction.

Original languageEnglish (US)
Pages (from-to)8752-8757
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number22
DOIs
StatePublished - May 29 2012

Keywords

  • Calcium imaging
  • Patch clamp

ASJC Scopus subject areas

  • General

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