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

Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L398-408. doi: 10.1152/ajplung.00299.2004. Epub 2004 Oct 29.


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 HCO(3)(-)-free solutions [at external pH (pH(o)) 7.4]. Cells were acid-loaded by the NH(4)(+) prepulse technique, and the recovery was observed. Under conditions designed to eliminate the contribution of other transporters that alter pH, addition of 10 microM ZnCl(2), 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 ZnCl(2) was observed at pH(o) 7.4 and pH(o) 8.0 and in normal and high-K(+) Ringer solutions. The observed rate of Zn(2+)-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 ZnCl(2) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acids / pharmacology
  • Animals
  • Cells, Cultured
  • Chlorides / pharmacology
  • Electrophysiology
  • Epithelial Cells / metabolism
  • Fluoresceins
  • Fluorescent Dyes
  • Hydrogen / metabolism*
  • Hydrogen-Ion Concentration / drug effects
  • Intracellular Membranes / metabolism*
  • Ion Channel Gating / physiology*
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / metabolism*
  • Isotonic Solutions / chemistry
  • Isotonic Solutions / pharmacology
  • Male
  • Models, Biological
  • Potassium / administration & dosage
  • Protons*
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Ringer's Solution
  • Zinc Compounds / pharmacology


  • Acids
  • Chlorides
  • Fluoresceins
  • Fluorescent Dyes
  • Ion Channels
  • Isotonic Solutions
  • Protons
  • Zinc Compounds
  • Hydrogen
  • Ringer's Solution
  • 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
  • zinc chloride
  • Potassium