Pinacidil-primed ATP-sensitive potassium channels mediate feedback control of mechanical power output in isolated myocardium of rats and guinea pigs.

We tested the hypothesis, that ATP-sensitive potassium (K(ATP)) channels limit cardiac energy demand by a feedback control of mean power output at increased cardiac rates. We analysed the interrelationships between rising energy demand of adult rat and guinea pig left ventricular papillary muscle and down-regulatory electromechanical effects mediated by K(ATP) channels. Using the K(ATP)-opener pinacidil the stimulation frequency was increased stepwise and the mechanical parameters and action potentials were recorded. Power output was derived from force-length area or force-time integral calculations, respectively. Simultaneously oxygen availability in the preparations was estimated by flavoprotein fluorescence measurements. ADP/ATP ratios were determined by HPLC. We found highly linear relationships between isotonic power output and the effects of pinacidil on isotonic shortening in both rat (r(2)=0.993) and guinea pig muscles (r(2)=0.997). These effects were solely observed for the descending limb of shortening-frequency relationships. In addition, a highly linear correlation between total force-time integral-derived power and pinacidil effects on action potential duration (APD(50), r(2)=0.92) was revealed. Power output became constant and frequency-independent in the presence of pinacidil at higher frequencies. In contrast, the K(ATP)-blocker glibenclamide produced a lengthening of APD(50) and increased force transiently at higher power levels. Pinacidil prevented core hypoxia and a change in ADP/ATP ratio during high frequency stimulation. We conclude, that pinacidil-primed cardiac K(ATP) channels homeostatically control power output during periods of high energy demand. This effect is associated with a reduced development of hypoxic areas inside the heart muscle by adapting cardiac function to a limited energy supply.