Cytosolic myocardial calcium modulation by ATP-dependent potassium channelopeners and NO donors

The goal of this study was to evaluate, in rat cardiomyocytes, the effects on cytosolic calcium of a pure K-adenosine triphosphate (ATP) channel opene r, aprikalim, and those of nicorandil, a dual-acting agent that increases c yclic guanosine monophosphate (cGMP) levels and opens K-ATP channels. These effects were compared with those of a pure NO donor, 3-morpholino-sydnonim ine (Sin-1). Ventricular myocytes were isolated from the hearts of adult ra ts. Changes in cytosolic calcium concentration ([Ca2+](i)) were measured by using a Ca2+ indicator, indo-1/AM. Alterations in indo-1 fluorescence were recorded during regular electrical stimulation. After 10 min of pacing, en d-diastolic [Ca2+](i) was significantly increased as compared with control without significant changes in calcium transient. For doses of 10(-7) to 10 (-4) M, aprikalim and nicorandil did not affect significantly the calcium t ransient. Sin-1 produced a significant decrease in calcium transient (by si milar to 20%), which was already maximal at 10(-7) M. When given with the p otassium channel antagonist glibenclamide (10(-5) M), nicorandil induced th e same effects as those observed with Sin-1. We conclude that potassium cha nnel openers aprikalim and nicorandil do not not decrease calcium transient . Thus the NO-donor properties of nicorandil are not apparent when given al one but appear when ATP-dependent potassium channels are blocked.