The Role of ATP-Sensitive Potassium Channels in Neutrophil Migration and Plasma Exudation

Neutrophil activation and migration during an inflammatory re-sponse is preceded or accompanied by plasma membrane electrical changes. Besides changes in calcium currents, neu-trophils have a high permeability to potassium, mainly through potassium channels. However, the significance of potassium channels in neutrophil physiology is still unclear. Here, we show that the treatment of rats with the ATP-sensitive potassium channel blocker glibenclamide (4, 20, or 40 mol/kg) dose dependently decreased carrageenan-, N-formyl-methionyl-leucyl-phenylalanine (fMLP)-, and lipopolysaccharide-induced neutrophil influx and fluid leakage into the interpleural space. On the other hand, minoxidil (an ATP-sensitive potassium channel opener; 25, 50, and 100 mol/kg) increased both neu-trophil influx and fluid leakage induced by a submaximal dose of carrageenan. In addition, in vitro human neutrophil chemo-taxis induced by leukotriene B4 or fMLP (both 1 M) was fully blocked by glibenclamide (10, 30, and 100 M) or tetraethyl-ammonium (a nonselective potassium channel blocker; 1, 3, and 10 mM). Thus, our results disclose the possibility that ATP-sensitive potassium channels may have a role in neutro-phil migration and chemotaxis and plasma exudation in the inflammatory response. Neutrophils are the most abundant polymorphonuclear leukocyte, constituting the main cell type involved in the nonimmune defense against pathogenic microorganisms. Al-though they have a protective effect, tissue damage observed in diseases such as rheumatoid arthritis, glomerulonephritis, immune vasculitis, and inflammatory bowel disease is also, at least in part, a consequence of neutrophil accumulatio