Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.

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Abstract
Background The efflux of potassium (K) through the ATP- sensitive K channel is considered an important cause of the rise in extracellular K ([K + ] e ) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K + ] e. Methods and Results We studied the effects of 10 and 25 μmol/L pinacidil, an ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K + ] e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 μmol/L unexpectedly lessened the rise in [K + ] e and the activation delay in both preparations. Pinacidil 10 μmol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K + ] e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage. Conclusions Our results indicate that the rise in [K + ] e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K + ] e by pinacidil reflects the balance of its effects on these several parameters.