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 [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 B_max value for cardiac [³H]glyburide binding sites, but decreased the if 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 [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 Ca²⁺-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.