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 Bmax value of [3H]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 for 9 days), did not alter the Bmax value for cardiac [3H]glyburide binding sites, but decreased the Bmax 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 [3H]glyburide binding in either heart or brain. Treatment with glyburide, pinacidil or hydralazine did not alter L-type calcium channels, assessed by [3H]PN 200 110 binding, in cardiac and brain membranes or small size Ca(2+)-activated K+ channels in brain assessed by [125I]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.