Vol. 300, Issue 3, 946-951, March 2002

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

José Eduardo Da Silva-Santos, Maria Cláudia Santos-Silva, Fernando de Queiroz Cunha and Jamil Assreuy

Department of Pharmacology (J.E.S.-S., J.A.) and Department of Clinical Analysis (M.C.S.-S.), Universidade Federal de Santa Catarina, Florianópolis Santa Catarina, Brazil; and the Department of Pharmacology, Faculty of Medicine of Ribeira Preto, Universidade de São Paulo, Brazil (F.Q.C.)

Neutrophil activation and migration during an inflammatory response is preceded or accompanied by plasma membrane electrical changes. Besides changes in calcium currents, neutrophils 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 µmol/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 µmol/kg) increased both neutrophil influx and fluid leakage induced by a submaximal dose of carrageenan. In addition, in vitro human neutrophil chemotaxis induced by leukotriene B₄ or fMLP (both 1 µM) was fully blocked by glibenclamide (10, 30, and 100 µM) or tetraethylammonium (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 neutrophil migration and chemotaxis and plasma exudation in the inflammatory response.