Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold

Xu Cao, Linlin Ma, Fan Yang, KeWei Wang, Jie Zheng

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)75-90
Number of pages16
JournalJournal of General Physiology
Volume143
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold'. Together they form a unique fingerprint.

  • Cite this