Expression and function of ATP-dependent potassium channels in late post-infarction remodeling.

Myocardial remodeling late after infarction is associated with increased incidence of fatal arrhythmias. Heterogeneous prolongation of the action potential in the surviving myocardium is one of the predominant causes. Sarcolemmal ATP-dependent potassium (K(ATP)) channels are important metabolic sensors regulating electrical activity of cardiomyocytes and are capable of considerably shortening the action potential. We determined whether ATP-dependent potassium channels generate or, on the contrary prevent the heterogeneity in action potential prolongation. Cardiomyocytes were obtained from the infarct border zone, the septum and the right ventricle of rat hearts 20 weeks after coronary occlusion when rats developed signs of heart failure. Expression of the conductance subunit Kir6.1, but not Kir6.2, and of all SUR regulatory subunits was increased up to 3-fold in cardiomyocytes from the infarct border zone. Concomitantly, there was a prominent response of the K(ATP) current to diazoxide that was not detectable in control cardiomyocytes. The action potential was prolonged in cardiomyocytes from the infarct border zone (74 ms) relative to sham (41 ms). However, activation of the K(ATP) channels by diazoxide reduced action potential duration to 42 ms. In myocytes of the septum and right ventricle, expression of channel subunits, duration of action potential, and sensitivity to diazoxide were only slightly increased relative to shams. In conclusion, the myocardium remodeled after infarction displays alterations of K(ATP) expression and function with spatial heterogeneity matching that of the action potential prolongation. Drugs selectively activating diazoxide-sensitive sarcolemmal K(ATP) channels should be considered in the prevention of arrhythmias in post-infarction heart failure.