Lactate activates ATP-sensitive potassium channels in guinea pig ventricular myocytes

The functional significance of cardiac ATP-sensitive potassium channels remains controversial because of the discrepancy between the low levels of ATP at which activation of the channels occurs and the much higher levels of ATP maintained during myocardial ischemia. We studied the effects of (+)-lactate, which accumulates in large quantity as a result of increased glycolysis during ischemia, on ATP-sensitive potassium channels in adult guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Lactate at 20-40 mM in the internal solution activated ATP-sensitive potassium channels and shortened action potential duration. Activation of the channels occurred even in the presence of 2-5 mM ATP in the internal solution and was dependent on intracellular free magnesium levels. Our results suggest that intracellular lactate may play a significant role in activating cardiac ATP-sensitive potassium channels and shortening action potential duration even at ATP levels similar to those resulting from moderate to severe myocardial ischemia.