The biophysical and molecular basis of TRPV1 proton gating.
EMBO J
; 30(6): 994-1002, 2011 Mar 16.
Article
in En
| MEDLINE
| ID: mdl-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.
Full text:
1
Database:
MEDLINE
Main subject:
Protons
/
Ion Channel Gating
/
TRPV Cation Channels
Limits:
Humans
Language:
En
Year:
2011
Type:
Article