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 Ca 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 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 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 2.3 in hearing physiology. Thus, we performed auditory profiling of Ca 2.3 controls, heterozygous Ca 2.3 mice and Ca 2.3 null mutants (Ca 2.3 ) using brainstem-evoked response audiometry. Interestingly, click-evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Ca 2.3 mice from both genders, whereas no alterations were observed in Ca 2.3 mice. Similar observations were made for tone burst-related ABRs in both genders. However, Ca 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 and W amplitude in mutant animals. In addition, alterations in W -W interwave interval were observed in female Ca 2.3 mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Ca 2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract.