温度感受性TRPチャネルの生理機能と創薬ターゲットとしての意義

抄録

Animals survive by detecting and adapting to the ambient temperatures. One of the important molecules involved in the temperature detection is TRP channel which consists of 28 members in 6 subfamilies in mammals. Eleven among the 28 TRP channels are activated by temperature changes, and thus called ‘thermosensitive TRP channels' Cation influx through temperature-sensitive channels like TRP channels causes some depolarization leads to activation of voltage-gated Na⁺ channels, followed by action potential generation. Because TRP channels have relatively high Ca²⁺ permeability, Ca²⁺ entering the cells activates Ca²⁺-activated Cl^- channels, causing further depolarization. Thermosensitive TRP channels are activated in the different temperature ranges and involved in various physiological phenomena in many species. I will introduce structures and functions of thermosensitive TRP channels together with significance of the complex of TRP channels and Ca²⁺-activated Cl^- channels, anoctamin 1. I will also discuss the TRP channels as potential drug targets. Furthermore, the evolutional aspects of thermosensitive TRP channels will be mentioned since animals are thought to have evolved by changing the expression and function of thermosensitive TRP channels through the changes in ambient temperatures.