Functional Implications Of Ca(V)2.3 R-Type Voltage-Gated Calcium Channels In The Murine Auditory System - Novel Vistas From Brainstem-Evoked Response Audiometry

Voltage-gated Ca2+ channels (VGCCs) are considered to play a key role in auditory perception and information processing within the murine inner ear and brainstem. In the past, Ca(v)1.3 L-type VGCCs gathered most attention as their ablation causes congenital deafness. However, isolated patch-clamp investigation and localization studies repetitively suggested that Ca(v)2.3 R-type VGCCs are also expressed in the cochlea and further components of the ascending auditory tract, pointing to a potential functional role of Ca(v)2.3 in hearing physiology. Thus, we performed auditory profiling of Ca(v)2.3(+/+) controls, heterozygous Ca(v)2.3(+/-) mice and Ca(v)2.3 null mutants (Ca(v)2.3(-/-)) using brainstem-evoked response audiometry. Interestingly, click-evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Ca(v)2.3(+/-) mice from both genders, whereas no alterations were observed in Ca(v)2.3(-/-) mice. Similar observations were made for tone burst-related ABRs in both genders. However, Ca(v)2.3 ablation seemed to prevent mutant mice from total hearing loss particularly in the higher frequency range (36-42 kHz). Amplitude growth function analysis revealed, i.a., significant reduction in ABR wave W-I and W-III amplitude in mutant animals. In addition, alterations in W-I-W-IV interwave interval were observed in female Ca(v)2.3(+/-) mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Ca(v)2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract.