Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold

Cao, Xu, Ma, Linlin, Yang, Fan, Wang, KeWei and Zheng, Jie (2014) Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold. Journal of General Physiology, 143 1: 75-90. doi:10.1085/jgp.201311025

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Author Cao, Xu
Ma, Linlin
Yang, Fan
Wang, KeWei
Zheng, Jie
Title Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold
Journal name Journal of General Physiology   Check publisher's open access policy
ISSN 0022-1295
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1085/jgp.201311025
Open Access Status File (Publisher version)
Volume 143
Issue 1
Start page 75
End page 90
Total pages 16
Place of publication New York, United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
Transient receptor potential vanilloid type 1 (TRPV1) channel responds to a wide spectrum of physical and chemical stimuli. In doing so, it serves as a polymodal cellular sensor for temperature change and pain. Many chemicals are known to strongly potentiate TRPV1 activation, though how this is achieved remains unclear. In this study we investigated the molecular mechanism underlying the gating effects of divalent cations Mg2+ and Ba2+. Using a combination of fluorescence imaging and patch-clamp analysis, we found that these cations potentiate TRPV1 gating by most likely promoting the heat activation process. Mg2+ substantially lowers the activation threshold temperature; as a result, a significant fraction of channels are heat-activated at room temperature. Although Mg2+ also potentiates capsaicin- and voltage-dependent activation, these processes were found either to be not required (in the case of capsaicin) or insufficient (in the case of voltage) to mediate the activating effect. In support of a selective effect on heat activation, Mg2+ and Ba2+ cause a Ca2+-independent desensitization that specifically prevents heat-induced channel activation but does not prevent capsaicin-induced activation. These results can be satisfactorily explained within an allosteric gating framework in which divalent cations strongly promote the heat-dependent conformational change or its coupling to channel activation, which is further coupled to the voltage- and capsaicin-dependent processes.
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Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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