Acute exposure to human interferon-alpha affects ion currents in human natural killer cells.
Interferon-alpha (IFN-alpha) is a particularly potent stimulator of human natural killer (NK) cell activity. The initial trigger for IFN action is not known, but there is indirect evidence from a number of cell types that changes in ion channel activity are among the earliest responses. Previous evidence includes changes in Ca2+ fluxes and intracellular activity, membrane potential changes, and effects of ion-channel blockers. Killing by human NK cells is dependent on external Ca2+ and on K+ channel activity. In the present study we have confirmed this dependence and the augmentation by human IFN-alpha. Then we directly studied the effects of IFN-alpha on ion currents in human NK cells using the patch-clamp electrophysiological techniques. We find that IFN-alpha can increase the predominant K+ current near the resting potential but suppresses it at higher voltages. Within 1 min after acute IFN-alpha treatment a new current is induced. This small current appears to be through nonselective cation channels that allow monovalent and divalent cations, including Ca2+ to permeate. This current presents a possible early triggering mechanism whereby acute exposure to IFN-alpha augments NK cytotoxicity.
Schlichter
L C
LC
Department of Physiology, University of Toronto, Toronto Western Hospital, Ont., Canada.
D002413:Cations, Divalent; D002470:Cell Survival / Q000187:drug effects; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects
D002413:Cations, Divalent; D016898:Interferon-alpha; D007473:Ion Channels; D015221:Potassium Channels