Interactive effects of Na and K in killing by human natural killer cells.
Contact-mediated lysis by human natural killer cells is inhibited by a number of drugs that block the predominant K channel. In this study we have further examined the role of the K channel and the interactions between passive K and Na transport in killing. Low external Na-inhibited killing and inhibition were not due to reduce inward current through the Na channels in the target cell. A role for the Na/H antiport is suggested since amiloride inhibited killing in a dose-dependent manner that was competitive with external Na. Depolarizing the killer cell with elevated external K did not inhibit killing. On the contrary, high K0 reduced the inhibition caused by low Na0 and by the K-channel blockers quinidine, verapamil, and retinoic acid. Hyperpolarizing the killer cell with low K0 or valinomycin inhibited killing. Valinomycin, which should prevent the depolarization caused by K-channel block, did not reverse the effect of the blockers quinidine, verapamil, and 4-aminopyridine. Hence, the primary role of the K channels during killing is not maintain the negative membrane potential. On the contrary, depolarization may promote killing under conditions where killing is submaximal.
Schlichter
L C
LC
Department of Physiology, University of Toronto, Ontario, Canada.
MacCoubrey
I C
IC
D000584:Amiloride / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers; D014634:Valinomycin / Q000494:pharmacology
D002352:Carrier Proteins; D015221:Potassium Channels; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D014634:Valinomycin; D000584:Amiloride; D012964:Sodium; D011188:Potassium