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The mechanism of Ca2+ independent activation of BKCa channels in mouse inner hair cells and the crucial role of the BK channels in auditory perception.
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2024-11-06 , DOI: 10.1016/j.jbc.2024.107970 Zhong-Shan Shen,Jun Gan,Bing Xu,Ya-Lin Chen,Fei-Fei Zhang,Jun-Wei Ji,Dan-Hua Chen,Yuehua Qiao,Qiong-Yao Tang,Zhe Zhang
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2024-11-06 , DOI: 10.1016/j.jbc.2024.107970 Zhong-Shan Shen,Jun Gan,Bing Xu,Ya-Lin Chen,Fei-Fei Zhang,Jun-Wei Ji,Dan-Hua Chen,Yuehua Qiao,Qiong-Yao Tang,Zhe Zhang
BK channels are expressed in mouse cochlear inner hair cells (IHCs) and exhibit Ca2+-independent activation at negative potentials. However, the mechanism underlying Ca2+-independent activation of the BK channels in mouse IHCs remains unknown. In this study, we found the BK channel expressed in IHCs contains both the STREX-2 (stress axis regulated exon) variant and an alternative splice of exon9 (alt9), which significantly shift the voltage dependence of the BK channels when co-expressed with LRRC52 in 0 [Ca2+]i. Furthermore, we discovered that mechanical force also induces negative shifts in the voltage dependence of IHC-expressed BK channels. Thus, we propose that the additive effects of mechanical force, special isoforms, and LRRC52 co-expression on voltage dependence shifts may account for the Ca2+-independent activation of the BK channel in IHC. Additionally, we found that the IHCs-specific deletion of the BK channels causes hearing damage in mice. Our study suggests a mechanism for Ca2+-independent activation in IHCs and highlights the crucial role of the BK channel in auditory perception.
更新日期：2024-11-06
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