Inhibition by protein kinase C of the KNDP subtype of vascular smooth muscle ATP-sensitive potassium channel

ATP-sensitive K+ channels (K-ATP) contribute to the regulation of tone in vascular smooth muscle cells. We determined the effects of protein kinase C (PKC) activation on the nucleoside diphosphate-activated (K-NDP) subtype of vascular smooth muscle K-ATP channel. Phorbol 12,13-dibutyrate (PdBu) and angiotensin II inhibited KNDP activity Of C-A patches of rabbit portal vein (PV) myocytes, but an inactive phorbol ester was without effect, and pretreatment with PKC inhibitor prevented the actions of PdBu. Constitutively active PKC inhibited K-NDP in I-O patches but was without effect in the presence of a specific peptide inhibitor of PKC. PdBu increased the duration of a long-lived interburst closed state but was without effect on burst duration or intraburst kinetics, PdBu treatment inhibited K-NDP, but not a 70-pS K-ATP channel of rat PV. The results indicate that the K-NDP subtype of vascular smooth muscle K-ATP channel is inhibited by activation of PKC. Control of K-NDP activity by intracellular signaling cascades involving PKC may, therefore, contribute to control of tone and arterial diameter by vasoconstrictors.