Chonnam Med J.  2009 Apr;45(1):38-46. 10.4068/cmj.2009.45.1.38.

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

• Piao LH
• Wu M
• Kim JH

• KMID: 2172282
• DOI: http://doi.org/10.4068/cmj.2009.45.1.38

Abstract

It is well known that opioid agonists are released from the myocardium during hypoxia or ischemia, and that ATP-sensitive potassium channels (K(ATP) 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 micron-opioid agonist DAMGO were examined on K(ATP) 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 micron mol/L) inhibited K(ATP) channel activities in a dose-dependent manner. K(ATP) channel activity, which had been attenuated by the addition of ATP (100 micron mol/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 micron mol/L. In the cell- attached patch configuration, however, DAMGO (1~300 micron mol/L) increased dinitrophenol (50 micron mol/L)- induced K(ATP) channel activities. It was inferred that the micron-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.

Keyword

micron-Opioid agonist; K(ATP) channels; Myocytes, Cardiac

MeSH Terms

Adenosine Triphosphate
Animals
Anoxia
Cell Membrane
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Felodipine
Ischemia
KATP Channels
Mice
Myocardium
Myocytes, Cardiac
Patch-Clamp Techniques
Potassium
Potassium Channels
Adenosine Triphosphate
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Felodipine
KATP Channels
Potassium
Potassium Channels

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