Vasoconstrictors inhibit ATP-sensitive K+ channels in arterial smooth muscle through protein kinase C

The effects of vasoconstrictor-receptor (neuropeptide Y, α-adrenergic, serotonergic, histaminergic stimulation on currents through ATP-sensitive potassium (K(ATP)) channels in arterial smooth muscle cells were examined. Whole-cell K(ATP) currents, activated by the synthetic K(ATP) channel opener pinacidil or by the endogenous vasolidator, calcitonin gene-related peptide, which acts through protein kinase A, were measured in smooth muscle cells isolated from mesenteric arteries of rabbit. Stimulation of NPY-, α1-, serotonin (5-HT2)-, and histamine (H1)-receptors inhibited K(ATP) currents by 40-56%. The signal transduction pathway that links these receptors to K(ATP) channels was investigated. An inhibitor of phospholipase C (D609) and of protein kinase C (GF 109203X) reduced the inhibitory effect of these vasoconstrictors on K(ATP) currents from 40-56% to H-23%. Activators of protein kinase C, a diacylglycerol analogue and phorbol 12-myristate 13- acetate (PMA), inhibited K(ATP) currents by 87.3 and 84.2%, respectively. K(ATP) currents, activated by calcitonin gene-related peptide, were also inhibited (47-87%) by serotonin, phenylephrine, and PMA. We propose that K(ATP) channels in these arterial myocytes are subject to dual modulation by protein kinase C (inhibition) and protein kinase A (activation).