Cardiac lysosomes and the mechanism of action of ouabain

Abstract

Cardiac glycosides are the main cardiotonic preparation used in the treatment of acute and chronic cardiac failure. So far, the mechanism underlying the effect of cardiac glycosides is not fully understood. It has been hypothesized that their effect is associated with inhibition of Na+,K+-ATPase in the cardiomyocyte plasma membrane [20]. Two binding sites for 3H-ouabain colocated with transport ATPase have been identified [9]. Other researchers believe that of Na§ is inhibited only by toxic doses of cardiac glycosides, and new glycoprotein with high affinity for ouabain does not depend on transport ATPase [11 ]. Cardiotonie effect of cardiac glycosides may be related to their interaction with intracellular structures [14]. Cardiac glycosides were detected in the area of contractile proteins, sarcoplasmic reticulum, and nucleus [10]. It was shown that the binding sites for 3H-ouabain on the plasma membrane of HeLa cells are cleared by dissociation of the ligand in the culture medium and by its internalization. Ouabain is located in lysosomes [3]. Similar results were obtained in experiments on isolated heart [18]. Cardiac lysosomes are involved in a number of important physiological processes, including autophagy, cardiomyocyte regeneration, endocytosis, and intracellular transport of drugs and hormones [2,8, 12,13,22]. They participate in the development of pathological processes. Increased permeability of lysosomal membranes and release of acid hydrolases in the cytosol may cause myocardial damage [23].