温度感受性TRPチャネルの活性制御機構

抄録

Among the huge TRP super family of ion channels, some have been proven to be involved in thermosensation. Insight into the molecular nature of temperature-gated ion channels came with the cloning of the capsaicin receptor, TRPV1 and the recognition that this ion channel protein could be activated by elevated temperatures with a threshold near 43°C. Three other TRPV channels, TRPV2, TRPV3 and TRPV4, have been cloned and characterized as thermosensors. The threshold temperatures for activation of these channels range from relatively warm (TRPV3 and TRPV4) to extremely hot (TRPV2). In contrast to the four heat-sensitive TRPV channels, TRPM8 and TRPA1, have been found to be activated by cold stimuli. Most of the mammalian thermosensitive TRP channels (thermoTRPs) identified to date can alternatively be activated by chemical stimuli, such as capsaicin for TRPV1. We found that temperature acts as a co-activator of thermoTRPs. In addition, thermoTRPs have various mechanisms for their functional regulation such as TRPV1 regulation through phosphorylation by PKC. Furthermore, we found that TRPM2, phylogenetically close to TRPM8, is a new thermoTRP activated by warm temperatures. We also found that TRPV4 needs other cytosolic proteins for its functional regulation. I summarize the recent progress in thermoTRPs research, especially about molecular mechanisms of their functional regulation by focusing on our own results. [J Physiol Sci. 2006;56 Suppl:S12]