Professor Eric Honoré

Molecular and Integrative Mechanobiology: Force-gated Ion Channels

Abstract

The conversion of force into an electrical cellular signal is mediated by the opening of different types of mechanosensitive ion channels (MSCs), including Piezo1/2 and TREK/TRAAK K2P channels. Mechanoelectrical transduction plays a key role in hearing, balance, touch, and proprioception and is also implicated in the autonomic regulation of blood pressure and breathing. Thus, dysfunction of MSCs is associated with a variety of inherited and acquired disease states. Significant progress has recently been made in identifying these channels, solving their structure, and understanding the gating of both hyperpolarizing and depolarizing MSCs. Besides prototypical activation by membrane tension, additional gating mechanisms involving channel curvature and/or tethered elements are at play. Moreover, our recent studies indicate a community effect between different structural and functional classes of mechanosensitive ion channels. Piezo1/2 ion channels are capable of conformational signaling and up-modulate the mechanical gating of K2P channels. I will discuss the structure-function properties of force-gated ion channels and their pathophysiological role.