Epicardial cells are more susceptible to the electrophysiological effects of ischemia than are endocardial cells. To explore the ionic basis for the differential electrophysiological responses to ischemia at the two sites, we used patch-clamp techniques to study the effects of ATP depletion on action potential duration and the ability of ATP-regulated K+ channels in single cells isolated from feline left ventricular endocardial and epicardial surfaces. During ATP depletion by treatment with 1 mM cyanide (CN-), shortening of action potential durations was significantly greater in epicardial cells than in endocardial cells. Thirty minutes after initiating exposure to 1 mM CN-, action potential duration at 90% repolarization was reduced to 0.70 ± 0.12 of the control value for endocardial cells versus 0.39 ± 0.18 for epicardial cells (p < 0.01), and action potential duration at 20% repolarization was reduced to 0.72 ± 0.13 for endocardial cells versus 0.12 ± 0.09 for epicardial cells (p < 0.01). In both endocardial and epicardial cells, the shortening of action potential by CN- treatment was partially reversed by 0.3 μM glibenclamide; the magnitude of reversal, however, was much greater in epicardial cells. After exposure to 1 mM CN-, the activity of ATP-regulated K+ channels in cell-attached membrane patches was significantly greater in epicardial cells than in endocardial cells. To study the dose-response relation between ATP concentration and open-state probability of the channels, intracellular surfaces of inside-out membrane patches containing ATP-regulated K+ channels were exposed to various concentrations of ATP (10-1,000 μM). The concentration of ATP that produced half-maximal inhibition of the channel was 23.6 ± 21.9 μM in endocardial cells and 97.6 ± 48.1 μM in epicardial cells (p < 0.01). These data indicate that ATP-regulated K+ channels are activated by a smaller reduction in intracellular ATP in epicardial cells than in endocardial cells. The differential ATP sensitivity of ATP-regulated K+ channels in endocardial and epicardial cells may be responsible for the differential shortening in action potentials during ischemia at the two sites.
- Adenosine triphosphate
- Single channels
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine