Loss of Potassium and Chloride Transport Changes PM-Induced Epithelial Dysfunction

Background: Chronic exposure to particulate matter (PM) is recognized as a significant contributor to respiratory health complications, including oxidative stress, inflammatory responses, and compromised epithelial barrier function. In this work, we ask whether the transport of potassium and chloride through the large-conductance calcium-activated potassium (BK Ca ) channel and the cystic fibrosis transmembrane conductance regulator (CFTR) channel may change PM-induced epithelial dysfunction. Methods: This study aimed to evaluate the impact of PM on cell variability, ROS level, inflammation, mitochondrial function, intracellular calcium homeostasis, and epithelial barrier integrity in three different airway epithelial cell lines: wild-type human bronchial epithelial cells (HBE WT), HBE WT cells with disruption of the KCNMA1 gene encoding the α-subunit of the BK Ca channel (HBE ΔαBK Ca ) with lost potassium transport, and cystic fibrosis bronchial epithelial cells (CFBE) with dysfunction of the chloride transport. Results: PM exposure significantly increased ROS synthesis and amplified IL-6 and TNF-α release, particularly in HBE ΔαBK Ca and CFBE cells. Mitochondrial function was also adversely affected, as evidenced by reduced maximal respiratory capacity in both HBE ΔαBK Ca and CFBE cells relative to HBE WT. In addition, PM-treated HBE ΔαBK Ca and CFBE cells showed higher intracellular calcium concentrations. Finally, PM exposure resulted in a pronounced reduction in transepithelial electrical resistance (TEER), with CFBE monolayers exhibiting the most significant susceptibility to barrier disruption. Conclusion: These findings indicate that impaired potassium and chloride transport through the BK Ca and CFTR channels exacerbates particulate matter–induced oxidative stress, inflammatory responses, mitochondrial dysfunction, and disturbances in calcium homeostasis in airway epithelial cells. Increased susceptibility of HBE ΔαBK Ca and CFBE cells to PM exposure, underscores the crucial role of proper ion transport in maintaining airway epithelial integrity. Keywords: particulate matter, potassium and chloride transport, oxidative stress, inflammation, mitochondrial function, epithelial barrier integrity