Schlichter L C, MacCoubrey I C
Department of Physiology, University of Toronto, Ontario, Canada.
Exp Cell Res. 1989 Sep;184(1):99-108. doi: 10.1016/0014-4827(89)90368-6.
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.
人类自然杀伤细胞的接触介导裂解受到多种阻断主要钾通道的药物的抑制。在本研究中，我们进一步研究了钾通道的作用以及被动钾和钠转运在杀伤过程中的相互作用。低细胞外钠抑制杀伤作用，而这种抑制并非由于靶细胞中通过钠通道的内向电流减少所致。由于氨氯地平以剂量依赖的方式抑制杀伤作用，且这种作用与细胞外钠具有竞争性，因此提示钠/氢反向转运体发挥了作用。用高细胞外钾使杀伤细胞去极化并不抑制杀伤作用。相反，高细胞外钾降低了低细胞外钠以及钾通道阻滞剂奎尼丁、维拉帕米和视黄酸所引起的抑制作用。用低细胞外钾或缬氨霉素使杀伤细胞超极化会抑制杀伤作用。缬氨霉素本应防止钾通道阻断所引起的去极化，但并未逆转奎尼丁、维拉帕米和4-氨基吡啶等阻滞剂的作用。因此，钾通道在杀伤过程中的主要作用并非维持膜的负电位。相反，在杀伤作用未达到最大程度的情况下，去极化可能会促进杀伤作用。
