exchanged for each calcium and that an increase in intracellular sodium concentration through this exchange mechanism leads to an increase in intracellular calcium concentration. As intracellular sodium increases, the concentration gradient driving sodium into the cell across the exchanger is reduced. As a result, the activity of the exchanger is reduced, which decreases the movement of calcium out of the cell. Thus by inhibiting the Na+/K+-ATPase, cardiac glycosides cause intracellular sodium concentration to increase. This leads to an accumulation of intracellular calcium via the Na+/Ca2+-exchange system with the following effects: In the heart, increased intracellular calcium causes more calcium to be released, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy). Inhibition of the Na+/K+-ATPase in vascular smooth muscle causes depolarization, which causes smooth muscle contraction. The conformational change of Na+/K+-ATPase plays not only a role in the contraction of muscles, but also in cell growth, cell motility and apoptosis. Due to de binding of cerberin, specific second messengers can be activated. After a cascade of cellular interactions nuclear transcription factors binds to the DNA and new enzymes will be made. This enzymes can for example play a role in cell proliferation.[subscription required] Efficacy There is very little formal, modern published information on the pharmacological actions of cerberin. One primary source reports that its ingestion results in electrocardiogram (ECG) changes, such as various types of bradycardia (e.g., sinus bradycardia), AV dissociation, and junctional rhythms; second-degree sinoatrial block and nodal rhythm are also described. In the case of digitalis administration, ST depression or T wave inversion may occur without indicating toxicity; however, PR interval prolongation indicate toxicity. Therapeutic uses There are no clearly established therapeutic uses of the title compound, cerberin. Digitalis compounds, related cardiac glycosides, function through the inhibition of the Na+/K+-ATPase-pump,[subscription required] and have been widely used for in the treatment of chronic heart failure and arrhythmias; although newer and more efficacious treatments for heart failure are available, digitalis compounds are still used. Some cardiac glycosides have been shown to have antiproliferative and apoptotic effects, and are therefore of interest as potential agents in cancer chemotherapy;[subscription required] there is a single report to date of possible antiproliferative activity of cerberin. Further reading References Cardiac glycosides Plant toxins