Transmembrane electrical potential difference regulates Na+/HCO3- cotransport and intracellular pH in hepatocytes

J. G. Fitz, S. D. Lidofsky, M. H. Xie, B. F. Scharschmidt

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


We have examined the hypothesis that a regulatory interplay between pH-regulated plasma membrane K+ conductance (gk+) and electrogenic Na+/HCO3- cotransport contributes importantly to regulation of intracellular pH (pHi) in hepatocytes. In individual cells, membrane depolarization produced by transient exposure to 50 mM K+ caused a reversible increase in pHi in the presence, but not absence, of HCO3-, consistent with voltage-dependent HCO3- influx. In the absence of HCO3-, intracellular alkalinization and acidification produced by NH4Cl exposure and withdrawal produced membrane hyperpolarization and depolarization, respectively, as expected for pHi-induced changes in gk+. By contrast, in the presence of HCO3-, NH4Cl exposure and withdrawal produced a decrease in apparent buffering capacity and changes in membrane potential difference consistent with compensatory regulation of electrogenic Na+/HCO3- cotransport. Moreover, the rate of pHi and potential difference recovery was several-fold greater in the presence as compared with the absence of HCO3-. Finally, continuous exposure to 10% CO2 in the presence of HCO3- produced intracellular acidification, and the rate of pHi recovery from intracellular acidosis was inhibited by Ba2+, which blocks pHi-induced changes in gK+, and by 4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid, which inhibits Na+/HCO3- cotransport. These findings suggest that in hepatocytes, changes in transmembrane electrical potential difference, mediated by pH-sensitive gK+, play a central role in regulation of pHi through effects on electrogenic Na+/HCO3- cotransport.

Original languageEnglish (US)
Pages (from-to)4197-4201
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - 1992


  • 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein
  • Ion transport
  • K conductance

ASJC Scopus subject areas

  • General


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