TY - JOUR
T1 - Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter
AU - Romero, Michael F.
AU - Hediger, Matthias A.
AU - Boulpaep, Emile L.
AU - Boron, Walter F.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/5/22
Y1 - 1997/5/22
N2 - Bicarbonate transporters are the principal regulators of pH in animal cells, and play a vital role in acid-base movement in the stomach, pancreas, intestine, kidney, reproductive system and central nervous system. The functional family of HCO3-transporters includes Cl--HCO3- exchangers, three Na+/HCO3- cotransporters, a K+/HCO3- cotransporter, and a Na+- driven Cl--HCO3- exchanger. Molecular information is sparse on HCO3- transporters, apart from Cl--HCO3- exchangers ('anion exchangers'), whose complementary DNAs were cloned several years ago. Attempts to done other HCO3- transporters, based on binding of inhibitors, protein purification or homology with anion exchangers, have so far been unsuccessful. Here we monitor the intracellular pH and membrane voltage in Xenopus oocytes to follow the expression of the most electrogenic transporter known: the renal 1:3 electrogenic Na+/HCO3- cotransporter from the salamander Ambystoma tigrinum. We now report the successful cloning and characterization of a cDNA encoding a cation-coupled HCO3- transporter. The encoded protein is 1,035 amino acids long with several potential membrane-spanning domains. We show that when it is expressed in Xenopus oocytes, this protein is electrogenic, Na+ and HCO3- dependent, and blocked by the anion-transport inhibitor DIDS, and conclude that it is the renal electrogenic sodium bicarbonate cotransporter (NBC).
AB - Bicarbonate transporters are the principal regulators of pH in animal cells, and play a vital role in acid-base movement in the stomach, pancreas, intestine, kidney, reproductive system and central nervous system. The functional family of HCO3-transporters includes Cl--HCO3- exchangers, three Na+/HCO3- cotransporters, a K+/HCO3- cotransporter, and a Na+- driven Cl--HCO3- exchanger. Molecular information is sparse on HCO3- transporters, apart from Cl--HCO3- exchangers ('anion exchangers'), whose complementary DNAs were cloned several years ago. Attempts to done other HCO3- transporters, based on binding of inhibitors, protein purification or homology with anion exchangers, have so far been unsuccessful. Here we monitor the intracellular pH and membrane voltage in Xenopus oocytes to follow the expression of the most electrogenic transporter known: the renal 1:3 electrogenic Na+/HCO3- cotransporter from the salamander Ambystoma tigrinum. We now report the successful cloning and characterization of a cDNA encoding a cation-coupled HCO3- transporter. The encoded protein is 1,035 amino acids long with several potential membrane-spanning domains. We show that when it is expressed in Xenopus oocytes, this protein is electrogenic, Na+ and HCO3- dependent, and blocked by the anion-transport inhibitor DIDS, and conclude that it is the renal electrogenic sodium bicarbonate cotransporter (NBC).
UR - http://www.scopus.com/inward/record.url?scp=0030926790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030926790&partnerID=8YFLogxK
U2 - 10.1038/387409a0
DO - 10.1038/387409a0
M3 - Article
C2 - 9163427
AN - SCOPUS:0030926790
SN - 0028-0836
VL - 387
SP - 409
EP - 413
JO - Nature
JF - Nature
IS - 6631
ER -