REGULATION OF ATP-SENSITIVE K+ CHANNELS BY CHRONIC GLYBURIDE AND PINACIDIL ADMINISTRATION

Treatment of rats with the K(ATP)+ channel antagonist sulfonylurea, glyburide (3 mg/kg/day, i.p., every 12 hr for 9 days). increased the B(max) value of [H-3]glyburide binding to heart and whole brain total membranes by 30 and 24 %, respectively. The ligand affinity was unaltered. Treatment with the K+ channel activator, pinacidil (20 mg/kg/day, i.p., every 12 hr tor 9 days), did not alter the B(max) value for cardiac [H-3]glyburide binding sites, but decreased the B(max) value in the brain by 21 %. Chronic administration of hydralazine, which caused an acute reduction in systolic blood pressure equivalent to that of pinacidil, did not alter [H-3]glyburide binding in either heart or brain. Treatment with glyburide, pinacidil or hydralazine did not alter L-type calcium channels, assessed by [H-3]PN 200 110 binding, in cardiac and brain membranes or small size Ca2+-activated K+ channels in brain assessed by [I-125]apamin binding. These studies show that the ATP-sensitive class of K+ channels can be regulated following chronic drug treatment in similar fashion to other receptor and channel systems.