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
Year: 2024
Type: article
Abstract: BK channels are expressed in mouse cochlear inner hair cells (IHCs) and exhibit Ca 2+ -independent activation at negative potentials. However, the mechanism underlying Ca 2+ -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 stress-axis regulated exon 2 variant and an alternative splice of exon9 (alt9), which significantly shift the voltage dependence of the BK channels when coexpressed with LRRC52 in 0 [Ca 2+ ] 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 coexpression on voltage dependence shifts may account for the Ca 2+ -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 Ca 2+ -independent activation in IHCs and highlights the crucial role of the BK channel in auditory perception.
Source: Journal of Biological Chemistry
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
Funders: National Natural Science Foundation of China, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Provincial Special Program of Clinical Medical Science, Xuzhou Science and Technology Program
OpenAlex ID: W4404094221