Inactivating Piezo1 Ion Channels

Tuesday, November 28, 2017

Research from Jason Wu in the Grandl Lab published in Cell Reports on November 28 explains how mechanosensitive Piezo1 ion channels inactivate.
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, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numerous human disease-related channelopathies that are not well-understood mechanistically. Here we identify the globular C-terminal extracellular domain as a structure that is sufficient to confer the time course of inactivation, and a single positively charged lysine residue at the adjacent inner pore helix as being required for its voltage dependence. Our results are consistent with a mechanism for inactivation that is mediated through voltage-dependent conformations of the inner pore helix and allosteric coupling with the C-terminal extracellular domain.