INDUCTION OF NITRIC-OXIDE (NO) SYNTHESIS IN MURINE MACROPHAGES REQUIRES POTASSIUM CHANNEL ACTIVITY

The activation of macrophages for antimicrobial responses is a multist age event involving numerous intracellular signalling cascades that ma kes possible target cell destruction by these effector cells. This stu dy examined the effects of different potassium channel inhibitors and activators on the NO production of murine macrophage-like cell lines P 388D.1 and B10-4(S). We found that the potassium channel inhibitors te traethylammonium, 4-aminopyridine, and quinine caused dose-dependent r eductions in the NO production of macrophages, and that the potassium channel activator, minoxidol, caused a dose-dependent enhancement of N O production. The inhibition of NO production was due to involvement o f potassium channels in the priming stage of macrophage activation, si nce pretreatment with the priming agent interferon-gamma partially res tored the NO response of the macrophages. The results of this study de monstrate a link between potassium channel activity and the activation of antimicrobial functions of murine macrophages.