**1. Introduction**

The cardiac glycosides are a class of drugs derived from the leaves of the *Digitalis purpurea* with a positive inotropic effect on the heart. For a very long time, they were successfully used as a primary treatment for congestive heart failure and arrhythmias [1]. The mechanism of action of the cardiotonic steroids in the human heart has been widely studied, and it is now accepted that it consists in the inhibition of the Na+/K+-ATPase—a transmembrane enzyme that regulates the gradient of sodium and potassium across the plasma membrane. It was assessed that the inhibition is made through the binding to a highly conserved extracellular recognition sequence of the Na+/K+ pump [2]. The favorable result of the use of the plant-derived cardiotonic steroids led to hypothesizing the existence of an endogenous cardiac glycoside counterpart in mammals and to assuming that its functional receptor might be the Na+/K+-ATPase [3]. This enzyme consists of an α- and a β-subunits. The α-subunit is made of 10 transmembrane segments that include, on the extracellular loops, the binding region for the cardiac glycoside, known as the ouabain-binding site. This region is highly conserved in the evolution among species from drosophila to rodents, sheep and humans [2,4].
