机械敏感通道TMEM63B参与背根神经节的有害热感觉
The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia
研究在背根神经节（DRG）神经元中考察机械敏感阳离子通道TMEM63B，意外发现其参与有害热感觉而非机械感觉。TMEM63B在DRG神经元中广泛表达，全身敲除或DRG特异性条件敲除均显著降低热敏感性，并减弱热诱导的钙反应和电流、升高动作电位触发温度阈值。重组TMEM63B在钙成像中表现出中等热反应，而在花生四烯酸存在下被热强烈激活，提示其热敏感性受膜脂环境调控。
by Chang Ye, Yan-Yu Zang, Gui-Fang Duan, Jiang Chen, Dan Wu, Dan Wang, Changlin Li, Yun Xu, Tianjiao Xia, Xiaoping Gu, Yun Stone Shi
In mammals, heat sensation is primarily mediated by thermosensitive channels, particularly transient receptor potential (TRP) channels, in dorsal root ganglion (DRG) neurons. However, whether additional channels contribute to noxious heat detection remains unclear. Here, we investigated the role of the mechanosensitive cation channel TMEM63B in DRG neurons and unexpectedly discovered its involvement in noxious thermosensation rather than mechanosensation. TMEM63B was broadly expressed in DRG neurons, and its global knockout or DRG-specific conditional knockout markedly reduced heat sensitivity. Deletion of TMEM63B significantly attenuated heat-induced calcium responses and currents in DRG neurons and elevated the temperature threshold for action potential initiation. Recombinant TMEM63B exhibited moderate heat response in calcium imaging assays. Notably, in the presence of arachidonic acid, TMEM63B was strongly activated by heat, suggesting that its thermosensitivity is modulated by the membrane lipid environment. Together, these findings identify TMEM63B as a novel channel contributing to heat sensation and reveal a lipid-dependent modulation of its channel activity.
来源：PLOS Biology · journals.plos.org