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 de pression (CSD)-associated hyperemia using the rat closed cranial window mod el. 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 i ncreased 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, c harybdotoxin (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 r ole in the CSD-associated hyperemia via an indomethacin-sensitive mechanism . NeuroReport 11:2103-2106 (C) 2000 Lippincott Williams & Wilkins.