Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells

Sci Adv. 2020 Apr 8;6(15):eaba1104. doi: 10.1126/sciadv.aba1104. eCollection 2020 Apr.

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 Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 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 Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cochlea / physiology
  • Electrophysiological Phenomena*
  • Hair Cells, Auditory, Outer / cytology*
  • Hair Cells, Auditory, Outer / physiology*
  • Humans
  • Ion Channel Gating
  • KCNQ Potassium Channels / metabolism*
  • Mechanical Phenomena*
  • Mice
  • Temperature

Substances

  • KCNQ Potassium Channels
  • Kcnq4 protein, mouse