BK(Ca) channel as a novel regulator of cellular DNA damage response in human bronchial epithelial cells in the presence of particulate matter.

While particulate matter (PM) is a well-studied genotoxic environmental agent, our understanding of the molecular mechanisms through which PM triggers its harmful health consequences remains insufficient. The respiratory epithelium serves as the primary site for the deposition of PM, thereby acting as a protective barrier. These epithelial cells are characterized by the presence of notable potassium channels, which are critical for the regulation of the fluid layer. In human bronchial epithelial cells (HBE), the large-conductance Ca(2+)-regulated potassium (BK(Ca)) channels, localized to the apical site of the plasma membrane, are critical for the maintenance of proper airway surface liquid volume. In this work, we focused on the role of the BK(Ca) channel and its potential role in DNA damage response (DDR) after PM exposure. The mechanisms of DDR have been extensively studied, however, the involvement of ion channels in this phenomenon is not known. Therefore, we used depleted for the BK(Ca) channel HBE cells (HBE Δα BK(Ca)) as a physiological model. We demonstrated that exposure to standardized PM in HBE Δα BK(Ca) cells induced reduced clone formation capabilities, an increase in ROS levels, PARP1-dependent apoptosis, cell cycle changes, and an increase in DNA double-strand breaks. A gene expression assessment by qPCR analysis revealed changes in expression levels of genes encoding proteins, especially from the DNA-single strand breaks repair pathway involved in oxidative DNA damage repair. Our findings imply that the absence of the BK(Ca) channel might weaken the cellular response to DNA damage, potentially making cells more susceptible to PM-induced genomic instability. In conclusion, our research indicates the novel role of the BK(Ca) channel in DDR for the first time.