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

被引：19

作者：

Perez-Flores, Maria C. ^{[1
]}

Lee, Jeong H. ^{[1
]}

Park, Seojin ^{[1
]}

Zhang, Xiao-Dong ^{[2
,3
]}

Sihn, Choong-Ryoul ^{[1
]}

Ledford, Hannah A. ^{[2
]}

Wang, Wenying ^{[1
]}

Kim, Hyo Jeong ^{[1
]}

Timofeyev, Valeriy ^{[2
,3
]}

Yarov-Yarovoy, Vladimir ^{[4
]}

Chiamvimonvat, Nipavan ^{[2
,3
]}

Rabbitt, Richard D. ^{[5
,6
,7
]}

Yamoah, Ebenezer N. ^{[1
]}

机构：

[1] Univ Nevada, Sch Med, Dept Physiol, Reno, NV 89557 USA

[2] Univ Calif Davis, Div Cardiol, Dept Internal Med, Davis, CA 95616 USA

[3] Northern Calif Hlth Care Syst, Dept Vet Affairs, Mather, CA 95655 USA

[4] Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA

[5] Univ Utah, Dept Biomed Engn, Salt Lake City, UT 84112 USA

[6] Univ Utah, Dept Otolaryngol, Salt Lake City, UT 84112 USA

[7] Univ Utah, Neurosci Program, Salt Lake City, UT 84112 USA

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 15期

关键词：

VOLTAGE; MOTILITY; PROTEIN; KCNQ4; AMPLIFICATION; TRANSDUCTION; BIOPHYSICS; PRESTIN; HEARING; MODEL;

D O I：

10.1126/sciadv.aba1104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(v)7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-K(v)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(v)7.4 channels mechanically sensitive, confirmed in consolidated K(v)7.4 channels at the base of OHCs. K(v)7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast K(v)7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies.

引用

页数：11