Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: The biophysical and molecular basis of TRPV1 proton gating.

Authors: Eduardo Aneiros, Lishuang Cao, Marianthi Papakosta, Edward B Stevens, Stephen Phillips, Christian Grimm

Journal, date & volume: EMBO J., 2011 Mar 16 , 30, 994-1002

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21285946

Abstract
The capsaicin receptor TRPV1, a member of the transient receptor potential family of non-selective cation channels is a polymodal nociceptor. Noxious thermal stimuli, protons, and the alkaloid irritant capsaicin open the channel. The mechanisms of heat and capsaicin activation have been linked to voltage-dependent gating in TRPV1. However, until now it was unclear whether proton activation or potentiation or both are linked to a similar voltage-dependent mechanism and which molecular determinants underlie the proton gating. Using the whole-cell patch-clamp technique, we show that protons activate and potentiate TRPV1 by shifting the voltage dependence of the activation curves towards more physiological membrane potentials. We further identified a key residue within the pore region of TRPV1, F660, to be critical for voltage-dependent proton activation and potentiation. We conclude that proton activation and potentiation of TRPV1 are both voltage dependent and that amino acid 660 is essential for proton-mediated gating of TRPV1.