Thermodynamic and structural bases for Yoda1-mediated Piezo1 activation

Abstract

The synthetic small molecule Piezo1-selective agonist Yoda1 is widely used to probe the biological functions of the mechanotransduction ion channel Piezo1. Yet, it is still unclear how Yoda1 activates Piezo1. Single-channel patch-clamp recordings reveal Piezo1 inherently populates at least four functional states, two conducting (open) and two non-conducting (shut). Yoda1 increases the dwell-time of a long-lived open state and shortens the dwell-time of other open and shut states, effectively increasing channel open probability (Po).