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, vascular smooth-muscle, neurons and fibroblasts; however, it is difficult to distinguish their Cl- 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, 55-57% identical to the electrogenic NBCs and 33-43% identical to the anion exchangers. 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.
Choi
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Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Aalkjaer
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C
Boulpaep
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Boron
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WF
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D019976:Cloning, Organism; D018076:DNA, Complementary; D004594:Electrophysiology; D006801:Humans; D008969:Molecular Sequence Data; D018075:RNA, Complementary; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D027982:Sodium-Bicarbonate Symporters; D014981:Xenopus
D001639:Bicarbonates; D002352:Carrier Proteins; D002712:Chlorides; D018076:DNA, Complementary; D018075:RNA, Complementary; D011994:Recombinant Proteins; D015222:Sodium Channels; D027982:Sodium-Bicarbonate Symporters; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid