1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
2. Department of Physiology and Danish Biomembrane Research Centre, University of Aarhus, Aarhus, DK-8000, Denmark

Correspondence to: Walter F. Boron¹ Correspondence and requests for materials should be addressed to W.F.B. (e-mail: Email: walter.boron@yale.edu). Sequences have been deposited in GenBank under accession numbers AF070475, AF069511 and AF080106 for NBCn1-B, NBCn1-C NBCn1-D, respectively.

Abstract

Two electroneutral, Na⁺-driven HCO^-₃ transporters, the Na⁺-driven Cl^-/HCO^-₃ exchanger and the electroneutral Na⁺/ HCO^-₃ cotransporter, have crucial roles in regulating intracellular pH in a variety of cells, including cardiac myocytes^{1, 2}, vascular smooth-muscle^{3, 4}, neurons⁵ and fibroblasts⁶; however, it is difficult to distinguish their Cl^- dependence in mammalian cells. Here we report the cloning of three variants of an electroneutral Na⁺/HCO^-₃ cotransporter, NBCn1, from rat smooth muscle. They are 89–92% identical to a human skeletal muscle clone⁷, 55–57% identical to the electrogenic NBCs and 33–43% identical to the anion exchangers⁸. When expressed in Xenopus oocytes, NBCn1-B (which encodes 1,218 amino acids) is electroneutral, Na⁺-dependent and HCO^-₃-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.