Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells
| Autor: | Xueling Wang, Chenchen Xia, Hao Wu, You Zhou, Yonghua Ji, Manli Yin |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Physiology Action Potentials Voltage-Gated Sodium Channels Gating Membrane Potentials Mice 03 medical and health sciences 0302 clinical medicine Hearing Hair Cells Auditory Extracellular Animals Humans Membrane potential Hair Cells Auditory Inner Chemistry Gene Expression Profiling General Neuroscience Sodium channel Alternative splicing General Medicine Cochlea Post-transcriptional modification Cell biology Mice Inbred C57BL Electrophysiology HEK293 Cells 030104 developmental biology Animals Newborn RNA editing Original Article 030217 neurology & neurosurgery |
| Zdroj: | Neurosci Bull |
| ISSN: | 1995-8218 1673-7067 |
| DOI: | 10.1007/s12264-019-00415-3 |
| Popis: | 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 (Nav1.1α–1.9α), among which Nav1.7α 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-019-00415-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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