The influence of zinc on the modulatory effect of sphingosylphosphorylcholine on Kv1.3 channels in human T lymphocytes.
In the present study, the whole-cell patch-clamp technique was applied to investigate the influence of co-application of zinc ions and sphingosylphosphorylcholine (SPC) on the SPC-induced shift of the activation midpoint and slowing of activation kinetics of Kv1.3 channels in human T lymphocytes. The results obtained provided evidence that the effects exerted by SPC and Zn were not additive. The shift was significantly diminished in a concentration-dependent manner upon co-application of 10 microM SPC and Zn in the concentration range 10-300 microM. However, the shift was not abolished in the presence of 100 and 300 microM of Zn co-applied with SPC. It was shown that the extent of the shift upon SPC and Zn co-application was similar to the shift observed for Zn applied without SPC. The slowing of the activation kinetics was also diminished upon SPC and Zn co-application; however, no clear dependence on concentration was observed. Moreover, the slowing was not abolished in the presence of 100 and 300 microM of Zn. It was shown that the slowing of the activation kinetics upon Zn and SPC co-application was primarily due to the effect exerted by SPC. The steepness of the voltage dependence of steady-state activation of the channels was not changed upon SPC and Zn co-application. Possible mechanisms underlying the observed phenomena and their possible physiological significance are discussed.
Teisseyre
Andrzej
A
Department of Biophysics, Wrocław Medical University, ul. Chałubińskiego 10, 50-368 Wrocław, Poland. ateiss@biofiz.am.wroc.pl.
Michalak
Krystyna
K
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051664:Kv1.3 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*
C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D015032:Zinc; D013110:Sphingosine