Evidence for independent Cl- and HCO3- secretion and involvement of an apical Na+-HCO3- cotransporter in cultured rat epididymal epithelia

Electrogenic chloride and bicarbonate secretion by cultured rat epididymal epithelia was studied using the short-circuit current (I-SC) technique. When incubated in normal solution, 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cpt-cAMP) caused a rise in the I-SC, which was attributable to Cl- and HCO3- secretion. Cl- secretion was found to contribute to the initial transient phase, whereas HCO3- secretion contributed to the sustained phase of the response. HCO3- secretion involves a basolaterally placed Na+-H+ exchanger and apical anion channel, most probably the cystic fibrosis transmembrane conductance regulator (CFTR). There is also evidence that an apical electrogenic Na+-HCO3- cotransporter is involved in HCO3- exit. CFTR accounted for 70% of HCO3- secretion, while the Na+-HCO3- cotransporter accounted for 30%. The possibility that the cotransporter may serve as an alternative pathway for HCO3- secretion in cystic fibrosis is discussed.