The Probable Pathway Of Intracellular Calcium Elevation Induced By Low Concentration Of Ouabain In Guinea Ventricular Mycytes

It is generally believed that cardiac glycosides (CGs) produce positive inotropic actions in failure heart via the inhibition of Na⁺,K⁺-ATPase activities, which results in the elevation of bulk intracellular Na⁺ concentration, and subsequent increase of intracellular Ca²⁺ concentration via Na⁺-Ca²⁺ exchange, thus increasing the uptake and subsequent release of Ca²⁺ by the sarcoplasmic reticulum (SR). However, the therapeutic concentrations (1-10nmol/l, low concentrations) of CGs to produce the positive inotropic effects in patients with congestive heart failure are much lower than those shown to inhibit the Na⁺,K⁺-ATPase in vitro (1-100 μ mol/l). Even some investigators found that the low concentrations of CGs could not inhibit, but stimulate the activity of the Na⁺,K⁺-ATPase in heart. Thus, the Na⁺,K⁺-ATPase inhibition theory of CGs seems to be insufficient to explain the therapeutic mechanism of CGs for the congestive heart failure at effective concentrations. Then, is the stimulation of the Na⁺,K⁺-ATPase a novel inotropic mechanism of low concentration of glycosides? Recently, studies revealed several previous unknown effects of ouabain on cardiac myocytes. Xie et al found that the some nontoxic...