Cytosolic Myocardial Calcium Modulation by ATP-Dependent Potassium Channel Openers 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 opener, aprikalim, and those of nicorandil, a dual-acting agent that increases cyclic guanosine monophosphate (cGMP) levels and opens K-ATP channels. These effects were compared with those of a pure NO donor, 3-morpholino-sydnonimine (Sin-1). Ventricular myocytes were isolated from the hearts of adult rats. Changes in cytosolic calcium concentration ([Ca]i) were measured by using a Ca indicator, indo-1/AM. Alterations in indo-1 fluorescence were recorded during regular electrical stimulation. After 10 min of pacing, end-diastolic [Ca]i was significantly increased as compared with control without significant changes in calcium transient. For doses of 10 to 10 M, aprikalim and nicorandil did not affect significantly the calcium transient. Sin-1 produced a significant decrease in calcium transient (by ∼20%), which was already maximal at 10 M. When given with the potassium channel antagonist glibenclamide (10 M), nicorandil induced the same effects as those observed with Sin-1. We conclude that potassium channel openers aprikalim and nicorandil do not not decrease calcium transient. Thus the NO-donor properties of nicorandil are not apparent when given alone but appear when ATP-dependent potassium channels are blocked.