INFLUENCE OF CARDIAC GLYCOSIDES ON CALCIUM BINDING IN MUSCLE SUBCELLULAR COMPONENTS

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

The influence of cardiac glycosides on the active Ca⁺⁺ transport mechanism of sarcoplasmic reticulum fragments (SRF) isolated from dog heart muscle and on the Ca⁺⁺ release from the SRF binding sites was studied. For this purpose, the free Ca⁺⁺ concentration in the medium containing SRF, murexide and other components such as MgCl₂, KCl and adenosine triphosphate was continuously recorded on an Aminco-Chance dual wavelength spectrophotometer employing 507-mµ and 470-mµ wavelengths. It was found that the Ca⁺⁺ transport mechanism of SRF is not influenced by cardiac glycosides. SRF prepared by the present method contained the following fractions of endogenous Ca⁺⁺ (in millimicromoles per milligram of protein): 1) "free" Ca⁺⁺ which is releasable in suspending medium, 3.0; 2) ethylenediamine tetraacetic acid (EDTA)-removable bound Ca⁺⁺, 6.1; 3) non-EDTA-removable bound Ca⁺⁺, 4.4. It was found that cardiac glycosides increased the amount of free releasable Ca⁺⁺ fraction of SRF. This Ca⁺⁺-releasing effect of cardiac glycosides was dose-dependent and had a positive correlation with the cardiotonic potency. From these findings, it is proposed that this Ca⁺⁺-releasing effect of cardiac glycosides may be related to the mechanism of inotropic effect of these drugs observed in vivo.