Glibenclamide enhances cortical spreading depression-associated hyperemia in the rat.
We investigated the contribution of ATP-sensitive potassium channels (K(ATP)) and calcium-activated potassium channels (Kca2+) to cortical spreading depression (CSD)-associated hyperemia using the rat closed cranial window model. The peak CBF response was enhanced by 12 +/- 5, 13 +/- 4, and 28 +/- 8% (p<0.01) of the control with 10(-6), 10(-5) and 10(-4) mol/l glibenclamide (glyb), a K(ATP) antagonist, respectively. We also calculated the area under the CBF curve to fully represent the extent of hyperemia during CSD. The area increased by 30 +/- 8 (p<0.05), 72 +/- 31 (p<0.05) and 88 +/- 20% (p<0.05) of the control with 10(-6), 10(-5) and 10(-4) mol/l glyb, respectively. However, charybdotoxin (CTX), a Kca2+ antagonist showed no effect. The effect of glyb was inhibited by pretreatment with 5 mg/kg indomethacin. We conclude that activation of K(ATP), perhaps associated with neurons, plays an inhibitory role in the CSD-associated hyperemia via an indomethacin-sensitive mechanism.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D018999:Charybdotoxin / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000502:physiology*; D005905:Glyburide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006940:Hyperemia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D005905:Glyburide; D007213:Indomethacin