The S2-S3 Loop of Kv7.4 Channels Is Essential for Calmodulin Regulation of Channel Activation.

ABSTRACT: Kv7.4 (KCNQ4) voltage-gated potassium channels control excitability in the inner ear and the central auditory pathway. Mutations in Kv7.4 channels result in inherited progressive deafness in humans. Calmodulin (CaM) is crucial for regulating Kv7 channels, but how CaM affects Kv7 activity has remained unclear. Here, based on electrophysiological recordings, we report that the third EF hand (EF3) of CaM controls the calcium-dependent regulation of Kv7.4 activation and that the S2-S3 loop of Kv7.4 is essential for the regulation mediated by CaM. Overexpression of the mutant CaM₁₂₃₄, which loses the calcium binding ability of all four EF hands, facilitates Kv7.4 activation by accelerating activation kinetics and shifting the voltage dependence of activation leftwards. The single mut

SUBMITTER: Zhuang W 

PROVIDER: S-EPMC7854705 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature