Influence of Thromboxane A(2) on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play an important role in myocardial protection. We examined the effects of thromboxane A(2) on the regulation of K(ATP) channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. RESULTS: In the excised inside-out patches, the thromboxane A(2) analog, U46619, decreased the K(ATP) channel activity in a dose-dependent manner; however, the thromboxane A(2) receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced K(ATP) channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced K(ATP) channel activity. CONCLUSION: Thromboxane A(2) may inhibit K(ATP) channel activity, and may have a harmful effect on ischemic myocardium.