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

Ciliated human nasal epithelial cells (c-hNECs) express the bicarbonate transport metabolon (BTM) consisting of carbonic anhydrase (CA) IV, Na + /HCO 3 - cotransporter (NBC) and CAII. This study demonstrated that the BTM rapidly and selectively transports HCO 3 - into c-hNECs resulting in a high intracellular pH (pH i ) in c-hNECs. Applying a CO 2 /HCO 3 - -free solution decreased ciliary beat frequency (CBF) at a high pH i , at which the CA-mediated reaction synthesized H + from CO 2 produced by the metabolism. An NH 4 + pulse also gradually decreased CBF and pH i following to immediate their increases in c-hNECs. Inhibition of NBC by S0859 decreased CBF and pH i , and the effects of the CO 2 /HCO 3 - -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), pH i in which was lower than that in c-hNECs, expressed CAII and NBC but not CAIV. In c-hBECs, the CO 2 /HCO 3 - -free solution transiently increased CBF and pH i and the NH 4 + pulse increased and plateaued CBF and pH i . Inhibition of NBC by S0859 did not decrease CBF and pH i in c-hBECs. Based on these observations, in c-hNECs, the interactions between CAIV and NBC play a key role to accelerate the HCO 3 - influx, acceleration of which increase pH i to an extremely high value. This novel mechanism keeping a high pH i maintains an adequate CBF in c-hNECs in the air (0.04% CO 2 ).