The role of the cochlea is to transduce complex sound signals into electrical neural activity in auditory nerve, with the help of hair cells responsible for the sensory of hearing. Hair cells undergo a precise developmental regulation when the promoter is spontaneous action potential (SAP) before sound-induced responses occur at the onset of hearing. Although SAP firing in inner hair cells (IHCs) is found to associate with a inward calcium current carried by the Cav1.3, a slow delayed rectifier potassium outward current and a small conductance Ca2+-activated K+ current SK2 to date,voltage-gated sodium channel (VGSCs) known as the major contributor for the rising phase of action potentials are less concerned. In the present study, the existence of all known subtypes of VGSCs (Nav1.1~Nav1.9) were revealed in cochlear basilar membrane . Sequence analysis of these cochlea-specific VGSCs indicated that some post-transcriptional events, e.g. alternative splicing and RNA-editing, resulting in scattered site mutations were frequently observed in the highly-organized assembly of the VGSCs motif. Functional characterization of these distinct mutants showed that single site mutation could lead to significant alterations in gating properties.
This study provide the first-handed evidences that VGSCs in cochlear basilar membrane could play an unique role in shaping spontaneous action potential in hearing system.