Association between Ca v 3 channel upregulation in spiral ganglion neurons and age-dependent hearing loss.

Ca _v 3 channels play a critical role in maintaining calcium homeostasis, and its dysregulation is related to age-related diseases, such as age-related hearing loss (AHL). However, the underlying mechanism of the Ca _v 3 channels involved in AHL remains unknown. Previous studies have shown that the degeneration of spiral ganglion neurons (SGNs) plays a critical role in AHL. Here, we explored the involvement of Ca _v 3 channels in the dysregulation of SGNs in AHL. We used C57BL/6 mice as the AHL mouse model and found that the expression of Ca _v 3 channels was increased in SGNs associated with age. The three subtypes of Ca _v 3 channels were present in the apical, middle, and basal SGNs from young and older (AHL) mice. The immunostaining data suggest that Ca _v 3.1 and Ca _v 3.2 may contribute to Ca _v 3 upregulation in SGNs of AHL mice. Additionally, we found that calpain-2 and apoptosis-inducing factor (AIF) were activated in SGNs from AHL mice. The inhibition of Ca _v 3 channels or calpain-2 reduced AIF-activation in SGNs may affect neuronal survival. In conclusion, the findings suggest that Ca _v 3 channels are upregulated in SGNs from AHL mice that may contribute to the degeneration of SGNs through the calpain-2-AIF apoptosis pathway in AHL mice.
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