The biophysical and molecular basis of TRPV1 proton gating
Open Access
- 1 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (6), 994-1002
- https://doi.org/10.1038/emboj.2011.19
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.Keywords
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