Abstract
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.
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