EFFECT OF CARDIAC GLYCOSIDES ON INTERACTION OF Ca⁺⁺ WITH MITOCHONDRIA

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

The influence of several cardiac glycosides with varying inotropic potencies of interaction of Ca⁺⁺ with mitochondria was studied. For this purpose, the Ca⁺⁺ transport mechanism of and Ca⁺⁺ binding to mitochondria were studied in the presence and absence of the cardiac glycosides. It was found that Ca⁺⁺ transport in dog heart mitochondria was not influenced, but Ca⁺⁺ binding to mitochondria was less in the presence of the active cardiac glycosides. Thus, the amount of Ca⁺⁺ released from dog heart mitochondria was increased in the presence of the active cardiac glycosides. However, the inactive cardiac glycosides had no affect on the Ca⁺⁺ release. The Ca⁺⁺-releasing effect of the cardiac glycosides was not observed in mitochondria obtained from rats or in "aged" dog heart mitochondria. The superprecipitation of cardiac actomyosin was delayed in the presence of mitochondria, and this delay was reversed when the active cardiac glycosides were also present. The potency of the reversal effect on superprecipitation approximately paralleled the cardiotonic potency of the glycosides. From these data, it was concluded that the Ca⁺⁺-releasing effect of the glycosides may contribute to the inotropic effect of these drugs observed in vivo.