ATP-Sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction

The role of ATP-sensitive potassium (K(ATP)) channels in modulating the action potential and contraction of guinea pig ventricular myocytes was investigated. Under voltage clamp, the maximum whole-cell K(ATP) channel conductance was estimated (195 ± 10 nS, n = 6) by exposing the cells to complete metabolic blockade (2 mM cyanide in the presence of 10 mM 2-deoxyglucose). In isolated inside-out membrane patches, the ATP dependence of K(ATP) channel activity under relevant conditions was measured (half-maximal inhibition at 114 μM). Under current clamp (with intracellular ATP concentration = 5 mM), the effect of graded K(ATP) channel activation on the action potential and the twitch was estimated by injection of a current (proportional to voltage) that simulated the K(ATP) conductance. As this 'conductance' was increased, the action potential was shortened, and contractile amplitude declined, as expected. From the results of these experiments, the quantitative dependence of the action potential duration on intracellular ATP concentration was estimated, without relying on a mathematical model of the cell membrane. The results imply that K(ATP)-dependent action potential shortening is likely to occur if ATP concentration falls below normal levels (~5 mM), as may happen regionally, or globally, during myocardial ischemia.