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 (K ATP channel) activity were examined in isolated cardiac ventricular myocytes. MATERIALS AND METHODS: K ATP 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 K ATP channel activity. In the presence of both ATP and ADP in the bath solution, the NO donors attenuated the activity of the K ATP channel. In cell-attached patches, the NO donors potentiated pinacidil-induced K ATP channel activity. In perforated whole-cell patch configuration, the NO donors decreased the K ATP current induced by PCO 400, a K ATP channel opener. PGI2 did not affect the K ATP channel activity in excised insideout patch. However, in the pres-ence of ATP in the internal solution, PGI2 increased the channel activity in a dose-dependent manner. In cell-attached patches, PGI2 did not only affect the channel activity itself, but also the dinitrophenol-induced K ATP channel activity. 11, 12-EET had no effect on K ATP 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 com-plicated, activation or inhibition, depending on the cellular environment.