PROTON CHANNELS, PLASMA-MEMBRANE POTENTIAL, AND RESPIRATORY BURST IN HUMAN NEUTROPHILS

When confronted with invading microorganisms, neutrophils undergo a nu mber of nearly synchronous reactions including the generation of micro bicidal reactive oxygen intermediates by the NADPH oxidase. These reac tions are accompanied by a slow depolarization, from resting values of - 60 mV to levels probably exceeding 0 mV. The depolarization is tran sient, indicating that a compensatory charge transport mechanism is ac tivated. Activation of the oxidase system causes a massive burst of me tabolic acid generation that would, if uncompensated, lower the intrac ellular pH of neutrophils by over 5 units, to lethal levels (pH = 2). Neutrophils must therefore possess particularly effective regulatory s ystems to avoid excessive cytosolic acidification. The recently descri bed H+ conductance of neutrophils may counteract both the acidificatio n and the depolarization. Activation of the H+ conductance occurs at d epolarizing voltages and is promoted by cytosolic acidification, a com bination that takes place during the respiratory burst. The NADPH oxid ase of neutrophils is thus associated to an unusual, particularly effi cient mechanism of H+ export and charge compensation. The sequential a ctivation of these two systems causes neutrophils to depolarize throug h the activation of an electron transport chain, and to repolarize thr ough the activation of a H+ conductance.