Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix

摘要: Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation is physiologically important, as it modulates overall sensitivity, gives rise to frequency filtering repetitive itself the target numerous human disease-related channelopathies not well understood mechanistically. Here, we identify globular C-terminal extracellular domain structure sufficient confer time course inactivation single positively charged lysine residue at adjacent inner pore helix being required its voltage dependence. Our results consistent with mechanism mediated conformations allosteric coupling domain.