Ciliary Motility Decreased by a CO2/HCO3−-Free Solution in Ciliated Human Nasal Epithelial Cells Having a pH Elevated by Carbonic Anhydrase IV

An application of CO₂/HCO₃^--free solution (Zero-CO₂) did not increase intracellular pH (pH_i) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in frequency (CBF) or amplitude (CBA) of the ciliary beating. This study demonstrated that the pH_i of c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while the pH_i of ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). An extremely high pH_i of c-hNECs caused pH_i, CBF and CBA to decrease upon Zero-CO₂ application, while a low pH_i of c-hBECs caused them to increase. An extremely high pH_i was generated by a high rate of HCO₃^- influx via interactions between CAIV and Na⁺/HCO₃^- cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased pH_i, CBF and CBA and increased CBF and CBA in c-hNECs upon Zero-CO₂ application. In conclusion, the interactions of CAIV and NBC maximize HCO₃^- influx to increase pH_i in c-hNECs. This novel mechanism causes pH_i to decrease, leading to no increase in CBF and CBA in c-hNECs upon Zero-CO₂ application, and appears to play a crucial role in maintaining pH_i, CBF and CBA in c-hNECs periodically exposed to air (0.04% CO₂) with respiration.