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.