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

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 dr...

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Bibliographic Details
Published in:Science advances 2020-04, Vol.6 (15), p.eaba1104
Main Authors: Perez-Flores, Maria C, Lee, Jeong H, Park, Seojin, Zhang, Xiao-Dong, Sihn, Choong-Ryoul, Ledford, Hannah A, Wang, Wenying, Kim, Hyo Jeong, Timofeyev, Valeriy, Yarov-Yarovoy, Vladimir, Chiamvimonvat, Nipavan, Rabbitt, Richard D, Yamoah, Ebenezer N
Format: Article
Language:English
Subjects:
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
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Summary: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 7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-K 7.4 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 7.4 channels mechanically sensitive, confirmed in consolidated K 7.4 channels at the base of OHCs. K 7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast K 7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aba1104