The role of ATP-sensitive potassium channels in neutrophil migration and plasma exudation.
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 micromol/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 micromol/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 microM) was fully blocked by glibenclamide (10, 30, and 100 microM) 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.
Da Silva-Santos
José Eduardo
JE
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis Santa Catarina, Brazil.
Santos-Silva
Maria Cláudia
MC
Cunha
Fernando de Queiroz
Fde Q
Assreuy
Jamil
J
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D005122:Exudates and Transudates / Q000166:cytology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels; D007958:Leukocyte Count; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D008914:Minoxidil; D019789:Tetraethylammonium; D005905:Glyburide