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

Maria C. Perez-Flores, Jeong H. Lee, Seojin Park, Xiao Dong Zhang, Choong Ryoul Sihn, Hannah A. Ledford, Wenying Wang, Hyo Jeong Kim, Valeriy Timofeyev, Vladimir Yarov-Yarovoy, Nipavan Chiamvimonvat, Richard D. Rabbitt, Ebenezer N Yamoah

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaba1104
JournalScience Advances
Volume6
Issue number15
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

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    Perez-Flores, M. C., Lee, J. H., Park, S., Zhang, X. D., Sihn, C. R., Ledford, H. A., Wang, W., Kim, H. J., Timofeyev, V., Yarov-Yarovoy, V., Chiamvimonvat, N., Rabbitt, R. D., & Yamoah, E. N. (2020). Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells. Science Advances, 6(15), [eaba1104]. https://doi.org/10.1126/sciadv.aba1104