Proton channels, plasma membrane potential, and respiratory burst in human neutrophils.
When confronted with invading microorganisms, neutrophils undergo a number of nearly synchronous reactions including the generation of microbicidal reactive oxygen intermediates by the NADPH oxidase. These reactions are accompanied by a slow depolarization, from resting values of-60 mV to levels probably exceeding 0 mV. The depolarization is transient, indicating that a compensatory charge transport mechanism is activated. Activation of the oxidase system causes a massive burst of metabolic acid generation that would, if uncompensated, lower the intracellular pH of neutrophils by over 5 units, to lethal levels (pH = 2). Neutrophils must therefore possess particularly effective regulatory systems to avoid excessive cytosolic acidification. The recently described H+ conductance of neutrophils may counteract both the acidification and the depolarization. Activation of the H+ conductance occurs at depolarizing voltages and is promoted by cytosolic acidification, a combination that takes place during the respiratory burst. The NADPH oxidase of neutrophils is thus associated to an unusual, particularly efficient mechanism of H+ export and charge compensation. The sequential activation of these two systems causes neutrophils to depolarize through the activation of an electron transport chain, and to repolarize through the activation of a H+ conductance.
Demaurex
N
N
Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
Schrenzel
J
J
Jaconi
M E
ME
Lew
D P
DP
Krause
K H
KH
D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D009504:Neutrophils / Q000502:physiology*; D017494:Proton Pumps / Q000502:physiology*; D016897:Respiratory Burst
D017494:Proton Pumps