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

Abstract

Recent studies have suggested that coronary endothelial cells produce and release nitric oxide (NO), prostaglandin I2, 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 I2, 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 I2 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 I2 activates only the K(drf) channels.