Effects of µ-Opioid Agonist on ATP-sensitive Potassium Channel Activity in Isolated Ventricular Cardiomyocytes

Abstract

It is well known that opioid agonists are released from the myocardium during hypoxia or ischemia, and that ATP-sensitive potassium channels (KATP channels) exist in the cardiac cell membrane and function as a cardioprotector preventing the myocardium from ischemic damage. In the present study, therefore, to determine whether opioid agonists are involved in the regulation of ATP-sensitive potassium channel activities, effects of the μ-opioid agonist DAMGO were examined on KATP channel activities by using excised inside-out and cell-attached patch clamp techniques in enzymatically (collagenase and protease) isolated mouse ventricular cardiac myocytes. In the excised inside-out patches, DAMGO (1∼300 μmol/L) inhibited KATP channel activities in a dose-dependent manner. KATP channel activity, which had been attenuated by the addition of ATP (100 μmol/L) to the internal solution, was not reactivated by DAMGO. The fashion of the single-channel inhibition by DAMGO was that both channel opening frequency and mean open-time were decreased, but the amplitudes of single channel currents and channel conductances were not altered. The half-maximal inhibition concentration (IC50) for DAMGO was 18 μmol/L. In the cellattached patch configuration, however, DAMGO (1∼300 μmol/L) increased dinitrophenol (50 μmol/L)induced KATP channel activities. It was inferred that the μ-opioid agonist is involved in the regulation of ATP-sensitive potassium channel activity in cardiac myocardium, agonizing (through internal target) or antagonizing (through external target) the inhibitory action of ATP in a competitive manner, thereby attenuating or enhancing the channel openings.