Functional implications of Ca_v 2.3 R-type voltage-gated calcium channels in the murine auditory system - novel vistas...

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.