Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells.

ABSTRACT: Voltage-gated sodium channels (VGSCs) are transiently expressed in cochlear hair cells before hearing onset and play an indispensable role in shaping spontaneous activity. In this study, we showed that Na⁺ currents shaped the spontaneous action potentials in developing mouse inner hair cells (IHCs) by decreasing the time required for the membrane potential to reach the action-potential threshold. In immature IHCs, we identified 9 known VGSC subtypes (Nav1.1?-1.9?), among which Nav1.7? was the most highly expressed subtype and the main contributor to Na⁺ currents in developing hair cells. Electrophysiological recordings of two cochlea-specific Nav1.7 variants (CbmNav1.7a and CbmNav1.7b) revealed a novel loss-of-function mutation (C934R) at the extracellular linker between segments 5 and 6 of domain II. In addition, post-transcriptional modification events, such as alternative splicing and RNA editing, amended the gating properties and kinetic features of CbmNav1.7a_(C934). These results provide molecular and functional characteristics of VGSCs in mammalian IHCs and their contributions to spontaneous physiological activity during cochlear maturation.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC6940418 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature