Nasal ciliary beating controlled by carbonic anhydrase IV and Na+/HCO3- co-transport under an extremely low CO2 condition (air)

Abstract

Ciliated human nasal epithelial cells (c-hNECs) express the bicarbonate transport metabolon (BTM) consisting of carbonic anhydrase (CA) IV, Na+/HCO3- cotransporter (NBC) and CAII. This study demonstrated that the BTM rapidly and selectively transports HCO3- into c-hNECs resulting in a high intracellular pH (pHi) in c-hNECs. Applying a CO2/HCO3--free solution decreased ciliary beat frequency (CBF) at a high pHi, at which the CA-mediated reaction synthesized H+ from CO2 produced by the metabolism. An NH4+ pulse also gradually decreased CBF and pHi following to immediate their increases in c-hNECs. Inhibition of NBC by S0859 decreased CBF and pHi, and the effects of the CO2/HCO3--free solution on CBF were reversed in c-hNECs pretreated with S0859 (i.e. it transiently increased CBF). Ciliated human bronchial epithelial cells (c-hBECs), pHi in which was lower than that in c-hNECs, expressed CAII and NBC but not CAIV. In c-hBECs, the CO2/HCO3--free solution transiently increased CBF and pHi and the NH4+ pulse increased and plateaued CBF and pHi. Inhibition of NBC by S0859 did not decrease CBF and pHi in c-hBECs. Based on these observations, in c-hNECs, the interactions between CAIV and NBC play a key role to accelerate the HCO3- influx, acceleration of which increase pHi to an extremely high value. This novel mechanism keeping a high pHi maintains an adequate CBF in c-hNECs in the air (0.04% CO2).