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This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/L398    most recent 00299.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Murphy, R. Articles by DeCoursey, T. E. Search for Related Content PubMed PubMed Citation Articles by Murphy, R. Articles by DeCoursey, T. E.

Voltage-gated proton channels help regulate pH_i in rat alveolar epithelium

Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois

Submitted 9 August 2004 ; accepted in final form 25 October 2004

Voltage-gated proton channels are expressed highly in rat alveolar epithelial cells. Here we investigated whether these channels contribute to pH regulation. The intracellular pH (pH_i) was monitored using BCECF in cultured alveolar epithelial cell monolayers and found to be 7.13 in nominally HCO₃^–-free solutions [at external pH (pH_o) 7.4]. Cells were acid-loaded by the NH₄⁺ prepulse technique, and the recovery was observed. Under conditions designed to eliminate the contribution of other transporters that alter pH, addition of 10 µM ZnCl₂, a proton channel inhibitor, slowed recovery about twofold. In addition, the pH_i minimum was lower, and the time to nadir was increased. Slowing of recovery by ZnCl₂ was observed at pH_o 7.4 and pH_o 8.0 and in normal and high-K⁺ Ringer solutions. The observed rate of Zn²⁺-sensitive pH_i recovery required activation of a small fraction of the available proton conductance. We conclude that proton channels contribute to pH_i recovery after an acid load in rat alveolar epithelial cells. Addition of ZnCl₂ had no effect on pH_i in unchallenged cells, consistent with the expectation that proton channels are not open in resting cells. After inhibition of all known pH regulators, slow pH_i recovery persisted, suggesting the existence of a yet-undefined acid extrusion mechanism in these cells.

proton conductance; pH regulation; hydrogen ion; acid load; 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein; intracellular pH

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