Action potential duration and activation of ATP-sensitive potassium current in isolated guinea-pig ventricular myocytes.
It is difficult to associate the ATP-sensitive potassium (K-ATP) channel of cardiac muscle with hypoxia/ischemia induced action potential shortening because this occurs before intracellular ATP falls to levels associated in vitro with channel opening. This leaves the cardiac K-ATP channel without any obvious physiological function. We have quantitatively examined the relationship between action potential duration and K-ATP channel activity in enzymatically isolated ventricular myocytes of the guinea-pig. In whole-cell voltage-clamp recording experiments when the K-ATP channel opener SR 44866 (2-10 microM) stimulated an outward membrane current greater than 50 pA at 0 mV membrane potential (the equivalent of 30 open K-ATP channels or 1% of the cell K-ATP channel population) action potential duration was reduced by more than 50%. In the majority of cell-attached membrane patch recordings metabolic inhibition stimulated K-ATP channel open probability of 1-2% which continued for long periods (7-25 min) before cell contracture and coincident major K-ATP channel activation (open probability 65%). Our quantitative analysis thus shows that physiologically relevant activity of K-ATP channels in cardiac muscle is confined to a very small percentage of the possible cell K-ATP current and thus intracellular ATP would not have to fall very far before the opening of K-ATP channels would influence cardiac excitability.
Faivre
J F
JF
Laboratoire de Physiologie Comparée (URA CNRS 1121), Université de Paris XI, Orsay, France.
Findlay
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D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*
D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; C061050:bimakalim; D000255:Adenosine Triphosphate; D011188:Potassium