Effects of Endothelium-derived Relaxing Factors on the Regulation of ATP-sensitive Potassium Channel Activity in Cardiac Myocytes

Abstract

Background and objectives:Effects of the three major endothelium-derived relaxing factors (EDRFs), namely nitric oxide (NO), prostacyclin (PGI2), and 11, 12-epoxyeicosatrienoic acid (EET) on the ATP-sensitive potassium channel (KATP channel) activity were examined in isolated cardiac ventricular myocytes. Materials and Methods:KATP channel activities were measured in the enzymatically (collagenase) isolated single mouse ventricular myocytes using excised inside-out, cell-attached, and perforated whole-cell patch clamp techniques. Results:In inside-out patches, NO donors, SNP and spermine NONOate, did not affect the KATP channel activity. In the presence of both ATP and ADP in the bath solution, the NO donors attenuated the activity of the KATP channel. In cell-attached patches, the NO donors potentiated pinacidil-induced KATP channel activity. In perforated whole-cell patch configuration, the NO donors decreased the KATP current induced by PCO 400, a KATP channel opener. PGI2 did not affect the KATP channel activity in excised inside-out patch. However, in the presence of ATP in the internal solution, PGI2 increased the channel activity in a dose-dependent manner. In cellattached patches, PGI2 did not only affect the channel activity itself, but also the dinitrophenol-induced KATP channel activity. 11, 12-EET had no effect on KATP channel activities. Conclusion:These results indicate that some of the endothelium-derived relaxing factors (nitric oxide and prostacyclin) are involved in the regulation of ATP-sensitive potassium channel activities in mouse ventricular myocytes;and the regulation type was complicated, activation or inhibition, depending on the cellular environment. (Korean Circulation J 2003;33 (5):420-430)