Cooperativity of K v 7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells

Abstract

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered K_v7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-K_v7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered K_v7.4 channels mechanically sensitive, confirmed in consolidated K_v7.4 channels at the base of OHCs. K_v7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast K_v7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies.