Protonation of the human PIEZO1 ion channel stabilizes inactivation

Abstract

Background: The mechanosensitive ion channel PIEZO1 opens when stress is applied to membranes. Results: PIEZO1 channel activation is inhibited at an extracellular pH of 6.3 with a pK of ≈6.9. Protonation is positively cooperative. Conclusion: Protonation stabilizes the inactivated state (not the closed state) of the channel. Significance: During physiological stress that gives rise to low pH, the PIEZO1 ion channel is inhibited.