Department of Neurobiology, Duke University Medical Center, Durham, NC.
J Gen Physiol. 2022 Jul 4;154(7). doi: 10.1085/jgp.202113044. Epub 2022 May 20.
Piezo ion channels are sensors of mechanical forces and mediate a wide range of physiological mechanotransduction processes. More than a decade of intense research has elucidated much of the structural and mechanistic principles underlying Piezo gating and its roles in physiology, although wide gaps of knowledge continue to exist. Here, we review the forces and energies involved in mechanical activation of Piezo ion channels and their functional modulation by other chemical and physical stimuli including lipids, voltage, and temperature. We compare the three predominant mechanisms likely to explain Piezo activation-the force-from-lipids mechanism, the tether model, and the membrane footprint theory. Additional sections shine light on how Piezo ion channels may affect each other through spatial clustering and functional cooperativity, and how substantial functional heterogeneity of Piezo ion channels arises as a byproduct of the precise physical environment each channel experiences. Finally, our review concludes by pointing out major research questions and technological limitations that future research can address.
压电离子通道是机械力的传感器，介导广泛的生理机械转导过程。经过十多年的深入研究，已经阐明了压电门控的结构和机械原理及其在生理学中的作用，尽管仍然存在广泛的知识空白。在这里，我们回顾了机械激活压电离子通道所涉及的力和能量，以及它们被其他化学和物理刺激（包括脂质、电压和温度）的功能调节。我们比较了三种可能解释 Piezo 激活的主要机制——力从脂质机制、系链模型和膜足迹理论。其他部分则阐明了压电离子通道如何通过空间聚类和功能协同作用相互影响，以及压电离子通道的显著功能异质性如何作为每个通道所经历的精确物理环境的副产品而产生。最后，我们的综述指出了未来研究可以解决的主要研究问题和技术限制。
