Abstract
Reactive oxygen species (ROS) appear to be involved in Fas-induced programmed cell death. We have previously demonstrated a tyrosine-kinase-dependent inhibition of the n-type K+ channels (Kn) by Fas stimulation. Thus, the effect of hydrogen peroxide (H2O2) on the function of Kn was examined using the patch-clamp technique. Incubation of Jurkat human T lymphocytes with 100 μM H2O2 resulted in a 46 ± 5% inhibition of the macroscopic whole-cell current. Experiments performed at the single-channel level using the cell-attached configuration revealed that the probability of the channel being open diminished upon incubation in H2O2. The effect was not dependent on src-like kinases, since H2O2 did not trigger tyrosine phosphorylation of the Kn channel protein and herbimycin A did not prevent channel inhibition. Kv1.3 channels underly the Kn of T lymphocytes and were expressed in Xenopus oocytes and subjected to electrophysiological analysis by the two-electrode voltage-clamp technique. Application of 1 mM H2O2 and 500 μM t-BOOH (tert, butylhydroperoxide) resulted in a marked inhibition of the K+ current within 20 min. Both the membrane-permeable thiol-group oxidizing agent DTNP [2,2′-dithiobis-(5-nitropyridine)] and the membrane-impermeable DTNB [5,5′-Dithiobis-(2-nitrobenzoic acid)] (50 μM) inhibited Kv1.3 channels, suggesting that extracellular domains of Kv1.3 are affected. These results point to a direct modulation of Kn by various oxidative agents.
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Received: 20 September 1996 / Received after revision and accepted: 29 November 1996
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Szabó, I., Nilius, B., Zhang, X. et al. Inhibitory effects of oxidants on n-type K+ channels in T lymphocytes and Xenopus oocytes. Pflügers Arch 433, 626–632 (1997). https://doi.org/10.1007/s004240050323
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DOI: https://doi.org/10.1007/s004240050323