Influence of vasoactive substances on the regulation of cardiac ATP-sensitive potassium channel activity

Background and Objectives: It has been known that various vasoactive agents are involved in the regulation of cardiac function through the modification of the K⁺ channel activities, including the ATP-sensitive K⁺ channel (K_ATP). We examined the effects of several vasoactive agents on the cardiac K_ATP currents in isolated cardiac myocytes. Materials and Methods: Ventricular myocytes were isolated from the hearts of ICR mice by enzymatic digestion. The channel currents were recorded by the excised inside-out and cell-attached patch clamp configurations. Results: In the excised inside-out patches, bradykinin (BRK; 1-10 μM) and prostaglandin I ₂ (PGI; 10-50 μM) did not affect the channel activities, whereas the vasodilators increased the attenuated channel activities in the presence of 100 μM ATP. BRK and PGI in parallel shifted the dose-response curves of ATP (1-1,000 μM), and this inhibited the K_ATP currents to the right. Endothelin (ET-1; 0.1-1 nM) and leukotriene D₄ (LTD; 3-10 μM) decreased the channel activities immediately after making the inside-out patches. However, the vasoconstrictors did not affect the attenuated channel activities by ATP. In the cell-attached patches, both BRK and PGI increased the channel activities and these effects were markedly attenuated by glibenclamide (50 μM). ET-1 and LTD did not affect the baseline channel activities in the cell-attached patches, but they markedly attenuated the dinitrophenol-induced activities. Conclusion: It was inferred that certain vasoactive substances are involved in the regulation of cardiac K_ATP channel activities, and that bradykinin and PGI₂ enhance the channel activities, and ET-1 and LTD4 inhibit the channel activities.