The electrogenic Na/HCO3 cotransporter

Walter F. Boron, Peying Fong, Matthias A. Hediger, Emile L. Boulpaep, Michael F. Romero

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The electrogenic Na/HCO3 cotransporter (symporter) is the major HCO3/- transporter of the renal proximal tubule (PT), located at the basolateral membrane (BLM), and also plays a noteworthy role in Na+ reabsorption. HCO3 transporters are important for regulation of intracellular pH (pH(i)) in most cells and also thereby regulate blood pH. This electrogenic Na/HCO3 cotransporter was first discovered using perfused Ambystoma tigrinum (salamander) renal, proximal tubules. This novel cotransporter mediates the movement of one Na+ ion with several HCO3/- ions, making it electrogenic, is blocked by stilbene compounds, but does not depend on intra- or extracellular Cl- . This and similar cotransporters have been found in a number of tissues and cell types. Recently, we used Xenopus laevis oocytes to expression clone the salamander renal electrogenic Na Bicarbonate Cotransporter (NBC). Using microelectrodes to monitor membrane potential (V(m)) and intracellular pH (pH(i)), we followed oocyte expresion after injecting poly (A)+, fractionated poly (A)+, or cRNA. All experimental solutions contained 100 μM ouabain to block the Na+/K+ pump. Our expression assay was to apply 1.5% CO2/10 mM HCO3/- (pH 7.5), allow pH(i) to stabilize from the CO2-induced acidification, and then remove bath Na+. Removing bath Na+ from native oocytes and water-injected controls, hyperpolarized the oocytes by ~ 5 mV and had no effect on phi(i). However, for oocytes injected with poly (A)+ RNA, removing Na+ transiently depolarized the cell by ~ 10 mV and caused pH(i) to decrease; both effects were blocked by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and required HCO3/-. Electrophoretic fractionation of the poly (A)+ RNA, enriched the expression signal. From the optimal expression-fraction, we constructed a size-selected cDNA library in pSPORT1. Screening our Ambystoma library yielded a single clone (aNBC). We could detect expression 3 days after injection of NBC cRNA. In aNBC-expresssing oocytes, adding CO2/HCO3/-elicited a large (> 50mV) and rapid hyperpolarization, followed by a partial relaxation as pH, stabilized. Na+ removal in CO2/HCO3/- depolarized the cell by >40mV and decreased pH(i), aNBC encodes a protein of 1035 amino acids with several putative membrane-spanning domains, and has a low level of amino-acid homology (~ 30% to the AE family of Cl-HCO3 exchangers. aNBC is the first member of a new family of Na+linked HCO3/- transporters and, together with the AE family, defines a new superfamily of HCO3/- transporters. Using aNBC to screen a rat-kidney cDNA library, we identified a full-length cDNA clone (rNBC), rNBC encodes a protein of 1035 amino acids, is 86% identical to aNBC, and can be functionally expressed in oocytes.

Original languageEnglish (US)
Pages (from-to)445-456
Number of pages12
JournalWiener Klinische Wochenschrift
Issue number12-13
StatePublished - 1997


  • Acid-base balance
  • Bicarbonate transport
  • Intracellular pH
  • Kidney
  • Proximal tubule

ASJC Scopus subject areas

  • General Medicine


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