An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel

Two electroneutral, Na+-driven HCO3- transporters, the Na+-driven Cl-/HCO3- exchanger and the electroneutral Na+/HCO3- cotransporter, have crucial roles in regulating intracellular pH in a variety of cells, including cardiac myocytes(1,2), vascular smooth-muscle(3,4), neurons(5) and fibroblasts(6); however, it is difficult to distinguish their CT dependence in mammalian cells. Here we report the cloning of three variants of an electroneutral Na+/HCO3- cotransporter, NBCn1, from rat smooth muscle. They are 89-92% identical to a human skeletal muscle clone(7), 55-57% identical to the electrogenic NBCs and 33-43% identical to the anion exchangers(8). When expressed in Xenopus oocytes, NBCn1-B (which encodes 1,218 amino acids) is electroneutral, Na+-dependent and HCO3--dependent, but not Cl--dependent. Oocytes injected with low levels of NBCn1-B complementary RNA exhibit a Na+ conductance that 4,4-diisothiocyanatostilbene-2,2'-disulphonate stimulates slowly and irreversibly.