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Deficiency of the BK Ca potassium channel displayed significant implications for the physiology of the human bronchial epithelium
Plasma membrane large-conductance calcium-activated potassium (BK ) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epithelial (HBE) cells also express BK in the inner mitochondrial membrane (mitoBK ). T...
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Published in: | Mitochondrion 2024-05, Vol.76, p.101880 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Plasma membrane large-conductance calcium-activated potassium (BK
) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epithelial (HBE) cells also express BK
in the inner mitochondrial membrane (mitoBK
). The genetic relationships between these mitochondrial and plasma membrane channels and the precise role of mitoBK
in epithelium physiology are still unclear. Here, we tested the hypothesis that the mitoBK
channel is encoded by the same gene as the plasma membrane BK
channel in HBE cells. We also examined the impact of channel loss on the basic function of HBE cells, which is to create a tight barrier. For this purpose, we used CRISPR/Cas9 technology in 16HBE14o- cells to disrupt the KCNMA1 gene, which encodes the α-subunit responsible for forming the pore of the plasma membrane BK
channel. Electrophysiological experiments demonstrated that the disruption of the KCNMA1 gene resulted in the loss of BK
-type channels in the plasma membrane and mitochondria. We have also shown that HBE ΔαBK
cells exhibited a significant decrease in transepithelial electrical resistance which indicates a loss of tightness of the barrier created by these cells. We have also observed a decrease in mitochondrial respiration, which indicates a significant impairment of these organelles. In conclusion, our findings indicate that a single gene encodes both populations of the channel in HBE cells. Furthermore, this channel is critical for maintaining the proper function of epithelial cells as a cellular barrier. |
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ISSN: | 1872-8278 |