Voltage-activated proton currents in human lymphocytes.
Voltage-activated proton currents are reported for the first time in human peripheral blood T and B lymphocytes and in the human leukaemic T cell line Jurkat E6-1. The properties of H(+) currents studied using tight-seal voltage-clamp recording techniques were similar in all cells. Changing the pH gradient by one unit caused a 47 mV shift in the reversal potential, demonstrating high selectivity of the channels for protons. H(+) current activation upon membrane depolarisation had a sigmoidal time course that could be fitted by a single exponential function after a brief delay. Increasing pH(o) shifted the activation threshold to more negative potentials, and increased both the H(+) current amplitude and the rate of activation. In lymphocytes studied at pH(i) 6.0, the activation threshold was more negative and the H(+) current density was three times larger than at pH(i) 7.0. Increasing the intracellular Ca(2+) concentration to 1 microM did not change H(+) current amplitude or kinetics detectably. Extracellularly applied Zn(2+) and Cd(2+) inhibited proton currents, slowing activation and shifting the voltage-activation curve to more positive potentials. The H(+) current amplitude was 100 times larger in CD19+ B lymphocytes and in Jurkat E6-1 cells than in CD3+ T lymphocytes. Following stimulation with the phorbol ester PMA, the H(+) current density in peripheral blood T lymphocytes and Jurkat T cells increased. In contrast, the H(+) current density of phorbol ester (PMA)-stimulated B lymphocytes was reduced and activation became slower. The pattern of expression of H(+) channels in lymphocytes appears well suited to their proposed role of charge compensation during the respiratory burst.
Schilling
Tom
T
Institute of Physiology, Humboldt University, Tucholskystrasse 2, D 10117 Berlin, Germany.
Gratopp
Alexander
A
DeCoursey
Thomas E
TE
Eder
Claudia
C
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism*; D010539:Permeability; D011522:Protons; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007473:Ion Channels; D011522:Protons; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium