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 journalArticle

16 Citations (Scopus)

Abstract

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
Volume89
Issue number9
StatePublished - 1992

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Membrane Potentials
Hepatocytes
Cell Membrane
Acidosis
Acids
Membranes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Transmembrane electrical potential difference regulates Na+/HCO3 - cotransport and intracellular pH in hepatocytes. / Fitz, J. G.; Lidofsky, S. D.; Xie, M. H.; Scharschmidt, B. F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 9, 1992, p. 4197-4201.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Xie, M. H.

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AB - 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.

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