Functional implications of Ca_v2.3 R‐type voltage‐gated calcium channels in the murine auditory system – novel vistas from brainstem‐evoked response audiometry

Abstract

Voltage-gated Ca 2+ 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, |LUNDT eT aL.

Breeding of Cav2.3 deficient mice reveals Mendelian inheritance in contrast to complex inheritance in Cav3.2 null mutant breeding

“…Ca v 2.3 breeding results and characteristics of inheritance. Ca v 2.3 mutant mice were bred for about eight years in different projects of our group (see 28,31,38,39,67 ). Ca v 2.3 +/+ , Ca v 2.3 +/− and Ca v 2.3 −/− mice were generated using three different breeding schemes, i.e., Ca v 2.3 +/− × Ca v 2.3 +/− , Ca v 2.3 +/− × Ca v 2.3 +/+ , and Ca v 2.3 +/− × Ca v 2.3 −/− .…”

“…Thus, the observed discrepancies between both inheritance studies might be based on the genetic specificities and the underlying strategies of genetic engineering of the mutant Ca v 2.3 model described by Alpodogan et al (2020) 66 and the Ca v 2.3 null mutant model that we used. The mutant Ca v 2.3 line which our study is based on, was the first Ca v 2.3 −/− model to be described in literature 100 and is widely used in the scientific community 31,38,39,101 . Based on the gene inactivation strategy in this model, the potential existence of a protein remnant/fragment, i.e., a truncated form of Ca v 2.3 cannot be fully ruled out.…”

“…Subsequently, PCR products were separated via agarose gel electrophoresis and detected by ChemiDoc Touch (Bio-Rad). For details on the procedure and genotyping results see also 28,31,38,39 . Note that genotyping of all experimental mice was carried out twice per animal (see supplementary tables 4-6) at the post weaning state.…”

Cation Permeability of Voltage-Gated Hair Cell Ca2+ Channels of the Vertebrate Labyrinth

“…The presence of a non-L Ca 2+ current component is also supported by the lack of vestibular deficits in the Ca v 1.3 null mice [ 26 ]. Nimodipine-insensitive Ca 2+ currents to be mediated via Ca v 2 channels were found in bullfrog saccular hair cells [ 15 ], and recent results have conclusively demonstrated that the R-type Ca v 2.3 Ca 2+ channels are mandatory for physiological auditory information processing [ 27 ]. Therefore, it is likely that R-type channels are present in hair cells of semi-circular canals as well; however, no molecular biology studies have conclusively demonstrated their presence, together with the well-established L-type channel.…”

Association Study of CACNA1E Gene Polymorphisms and Sudden Sensorineural Hearing Loss

“…이와 같이 청력과 VGCC와의 연관성을 알아보기 위해 많 은 연구들이 진행되었다. [13][14][15][16][17][18][19][20][21] 내이와 청각 경로 발현에 관여 하는 VGCC 복합체는 주로 Cav1.3 L-형과 Cav2.3 R-형이 관 여한다. 14,15) 그중 Cav1.…”