Downregulation of KCNMA1 in mice accelerates auditory hair cells senescence via ferroptosis

Abstract

KCNMA1 encodes the K+ potassium channel α-subunit that plays a significant role in the auditory system. Our previous studies indicated that KCNMA1 is associated with age-related hearing loss(AHL). However, the detailed mechanism of KCNMA1 involvement in auditory age-related degradation has not been fully clarified. Therefore, we explored the expression of KCNMA1 in the peripheral auditory of 2-month-old and 12-month-old mice by Western blotting and immunofluorescence. The results of animal experiments showed that KCNMA1 expression was decreased in 12-month-old mice compared with 2-month-old mice, whereas the ferroptosis level was increased. To verify the role of KCNMA1 in AHL, we downregulated KCNMA1 in HEI-OC1 cells by transfecting shRNA. After downregulation, the ferroptosis level was increased and the aging process was accelerated. Furthermore, the aging process was affected by the expression of ferroptosis. In conclusion, these results revealed that KCNMA1 is associated with the aging process in auditory hair cells by regulating ferroptosis, which deepens our understanding of age-related hearing loss.

Keywords: Age-related hearing loss; Auditory hair cell; Ferroptosis; KCNMA1; Mitochondria.