Induction of nitric oxide (NO) synthesis in murine macrophages requires potassium channel activity.
The activation of macrophages for antimicrobial responses is a multistage event involving numerous intracellular signalling cascades that makes possible target cell destruction by these effector cells. This study examined the effects of different potassium channel inhibitors and activators on the NO production of murine macrophage-like cell lines P388D.1 and B10-4(S). We found that the potassium channel inhibitors tetraethylammonium, 4-aminopyridine, and quinine caused dose-dependent reductions in the NO production of macrophages, and that the potassium channel activator, minoxidol, caused a dose-dependent enhancement of NO production. The inhibition of NO production was due to involvement of potassium channels in the priming stage of macrophage activation, since pretreatment with the priming agent interferon-gamma partially restored the NO response of the macrophages. The results of this study demonstrate a link between potassium channel activity and the activation of anitimicrobial functions of murine macrophages.
Lowry
M A
MA
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Goldberg
J I
JI
Belosevic
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; D019789:Tetraethylammonium; D011803:Quinine; D015761:4-Aminopyridine