Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold | |
Cao, Xu ; Ma, Linlin ; Yang, Fan ; Wang, KeWei ; Zheng, Jie | |
刊名 | journal of general physiology
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2014 | |
关键词 | CAPSAICIN RECEPTOR TRPV1 EXTERNAL PROTONATION SITES 2 INACTIVATION MECHANISMS ROOT GANGLION NEURONS POTASSIUM CHANNELS ION-CHANNEL K+ CHANNEL VANILLOID RECEPTOR-1 PROTEIN-KINASE PORE TURRET |
DOI | 10.1085/jgp.201311025 |
英文摘要 | 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- nd 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.; Physiology; SCI(E); PubMed; 7; ARTICLE; wangkw@bjmu.edu.cn; jzheng@ucdavis.edu; 1; 75-90; 143 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/323024] ![]() |
专题 | 心理与认知科学学院 |
推荐引用方式 GB/T 7714 | Cao, Xu,Ma, Linlin,Yang, Fan,et al. Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold[J]. journal of general physiology,2014. |
APA | Cao, Xu,Ma, Linlin,Yang, Fan,Wang, KeWei,&Zheng, Jie.(2014).Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold.journal of general physiology. |
MLA | Cao, Xu,et al."Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold".journal of general physiology (2014). |
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