Regulation of potassium channels in coronary arterial smooth muscle by endothelium-derived vasodilators

Recent studies have suggested that coronary endothelial cells produce and release nitric oxide (NO), prostaglandin I-2, and epoxyeicosatrienoic acids (EETs). These endothelium-derived vasodilators play an important role in the control of coronary vascular tone. However, the mechanism by which these endothelium-derived vasodilators cause relaxation of coronary arterial smooth muscle has yet to be determined. This study characterized and compared the effects of NO, prostaglandin I-2, and 11,12-EET on the two main types of potassium Channels in small bovine coronary arterial smooth muscle: the large conductance Ca2+-activated K+ channels (K-Ca) and 4-aminopyridine-sensitive delayed rectifier K+ channels (K-drf) In cell-attached patches, nonoate, an NO donor, activated both K-Ca and K-drf channels. The open probability of both K-Ca and K-drf channels increased 10- to 25-fold when nonoate was added to the bath at concentrations of 10(-6) to 10(-4) mol/L. 11,12-EET (10(-8) to 10(-4) mol/L) also increased the activity of the K-Ca channels in a concentration-dependent manner, but it had no effect on the activity of the K-drf channels, even in the highest concentration studied (10(-4) mol/L). In contrast to the effect of 11,12-EET, iloprost, a prostaglandin I-2 analogue (10(-6) to 10(-4) mol/L), produced a concentration-dependent increase in the activity of K-drf channels without affecting the K-Ca channels. In conclusion, all three endothelium-derived vasodilators act to open potassium channels; however, the channel types that they affect are different. NO activates both K-Ca and K-drf channels; 11,12-EET activates only the K-Ca channels; and prostaglandin It activates only the K-drf channels.