Positive Inotropic Action of Digitalis and Endogenous Factors: Na,K-ATPase and Positive Inotropy; 'Endogenous Glycosides'

Publisher Summary This chapter describes the positive inotropic action of digitalis and endogenous factors: Na,K-ATPase and positive inotropy and endogenous glycoside. It is suggested that progress have been made in understanding how cardiac glycosides produce their powerful stimulating action on cardiac contraction. The evidence to date suggests strongly that the Na,K-ATPase is the pharmacological receptor, or if there are multiple mechanisms, one of the pharmacological receptors. It appears that inhibition of Na,K-ATPase enzyme activity and subsequent increase in the activity of Na ion at the inside of the sarcolemmal membrane that in turn activates a Na/Ca exchange “carrier,” represents the sequence of changes that lead from a binding of digitalis to the Na,K-ATPase, to the positive inotropic action. The critical experiments that are now needed to solidify this hypothesis must involve simultaneous measurements of aNai and aCai, contraction, and digitalis binding to Na,K-ATPase and to other suggested sites. These experiments are certainly not easy. They require a relatively simple type of cardiac preparation, such as viable single cells devoid of fibroblasts, in which contraction can be quantitatively measured. The possibility that endogenous substances exist that regulate the pump by an action on the outside of the sarcolemma is very exciting.