Piezo2 voltage-block regulates mechanical pain sensitivity
biorxiv(2022)
摘要
PIEZO2 mechanosensitive channels are required for normal touch sensation. However, PIEZO2 channels are almost completely blocked at negative resting membrane potentials. We show that PIEZO2 voltage-block can be relieved by mutations at a conserved Arginine (R2756) which dramatically sensitizes the channel to mechanical stimuli. We generated Piezo2 R2756H/R2756H and Piezo2 R2756K/R2756K knock-in mice to ask how voltage regulates the endogenous mechanosensitivity of sensory neurons. Surprisingly, mechanosensitive currents in nociceptors, neurons that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but touch receptors were largely unaffected. Piezo2 knock-in mice were hypersensitive to noxious mechanical stimuli as their nociceptors acquired properties similar to ultrasensitive touch receptors. Thus, mechanical pain sensitivity can be tuned by voltage-block of PIEZO2 channels, a channel property potentially amenable for pharmacological modulation.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
关键词
mechanical pain sensitivity,voltage-block
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要