Cav3.2 T-Type Calcium Channels Are Physiologically Mandatory for the Auditory System

Abstract

Voltage-gated Ca²⁺ channels (VGCCs) play key roles in auditory perception and information processing within the inner ear and brainstem. Pharmacological inhibition of low voltage-activated (LVA) T-type Ca²⁺ channels is related to both age- and noise induced hearing loss in experimental animals and may represent a promising approach to the treatment of auditory impairment of various etiologies. Within the LVA Ca²⁺ channel subgroup, Ca_v3.2 is the most prominently expressed T-type channel entity in the cochlea and auditory brainstem. Thus, we performed a complete gender specific click and tone burst based auditory brainstem response (ABR) analysis of Ca_v3.2^+/- and Ca_v3.2^-/- mice, including i.a. temporal progression in hearing loss, amplitude growth function and wave latency analysis as well as a cochlear qPCR based evaluation of other VGCCs transcripts. Our results, based on a self-programmed automated wavelet approach, demonstrate that both heterozygous and Ca_v3.2 null mutant mice exhibit age-dependent increases in hearing thresholds at 5 months of age. In addition, complex alterations in W_I-IV amplitudes and latencies were detected that were not attributable to alterations in the expression of other VGCCs in the auditory tract. Our results clearly demonstrate the important physiological role of Ca_v3.2 VGCCs in the spatiotemporal organization of auditory processing in young adult mice and suggest potential pharmacological targets for interventions in the future.

Keywords: T-type; auditory brainstem response; calcium channel; hair cells; sensorineural hearing loss; spiral ganglion neuron.