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Original Article

Botond Bánfi^a,c, Jacques Schrenzel^a, Oliver Nüsse^a, Daniel P. Lew^a, Erzsébet Ligeti^c, Karl-Heinz Krause^b, and Nicolas Demaurex^d

^a From the Division of Infectious Diseases, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
^b From the Department of Geriatrics, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
^c Department of Physiology, Semmelweis Medical University, H-1444 Budapest, Hungary
^d Department of Physiology, University of Geneva, CH-1211 Geneva 4, Switzerland
Department of Physiology, University of Geneva Medical Center, 1, Michel-Servet, CH-1211 Geneva 4, Switzerland.41-22-702-540241-22-702-5399

Nicolas.Demaurex{at}medecine.unige.ch

Efficient mechanisms of H⁺ ion extrusion are crucial for normal NADPH oxidase function. However, whether the NADPH oxidase—in analogy with mitochondrial cytochromes—has an inherent H⁺ channel activity remains uncertain: electrophysiological studies did not find altered H⁺ currents in cells from patients with chronic granulomatous disease (CGD), challenging earlier reports in intact cells. In this study, we describe the presence of two different types of H⁺ currents in human eosinophils. The "classical" H⁺ current had properties similar to previously described H⁺ conductances and was present in CGD cells. In contrast, the "novel" type of H⁺ current had not been described previously and displayed unique properties: (a) it was absent in cells from gp91- or p47-deficient CGD patients; (b) it was only observed under experimental conditions that allowed NADPH oxidase activation; (c) because of its low threshold of voltage activation, it allowed proton influx and cytosolic acidification; (d) it activated faster and deactivated with slower and distinct kinetics than the classical H⁺ currents; and (e) it was 20-fold more sensitive to Zn²⁺ and was blocked by the histidine-reactive agent, diethylpyrocarbonate (DEPC). In summary, our results demonstrate that the NADPH oxidase or a closely associated protein provides a novel type of H⁺ conductance during phagocyte activation. The unique properties of this conductance suggest that its physiological function is not restricted to H⁺ extrusion and repolarization, but might include depolarization, pH-dependent signal termination, and determination of the phagosomal pH set point.

Key Words: proton conductance • NADPH oxidase • granulomatous disease • hydrogen ion concentration • eosinophils

J. Schrenzel's present address is Department of Clinical Microbiology, Mayo Clinic, Rochester, MN.

© 1999 The Rockefeller University Press

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This article has been cited by other articles:

• Cherny, V. V., DeCoursey, T. E. (1999). Ph-Dependent Inhibition of Voltage-Gated H+ Currents in Rat Alveolar Epithelial Cells by Zn2+ and Other Divalent Cations. JGP 114: 819-838 [Abstract] [Full Text]  

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