Evidence for two kinetically and functionally different types of cardiac glycoside receptors in the heart

Abstract

Cardiac glycosides bind with high affinity to specific receptors in the heart. In cardiac cell membranes of most animal species and man, this glycoside-receptor binding is followed by a subsequent inhibition of the membranebound (Na⁺ +K⁺)-ATPase, the biochemical equivalent of the active Na⁺/K⁺-transport system. Most investigators, however, have been unable to find, as a consequence of the glycoside-(Na⁺ +K⁺)-ATPase interaction, an inhibited Na⁺ or K⁺ transport in intact cardiac tissue when using low but positive inotropic concentrations of cardiac glycosides. In electrically stimulated contracting rat or guinea pig cardiac muscle we determined two kinetically diffrerent ³H-ouabain binding sites. The high afinity/low capacity site is related to positive inotropy, whereas the low afinity/high capacity binding site is connected to an inhibition of the (Na⁺ +K⁺)-ATPase. Occupation of the low affinity sites with ouabain molecules was concomitant with an increased intracellular Na⁺ and loss of K⁺ as well as onset of arrhythmias. According to our experiments, there are at least two different types of ouabain binding sites, inhibition of the (Na⁺ +K⁺)-ATPase was not necessarily related to positive inotropy in rat and guinea pig heart.

Digitalis receptors, ouabain, positive inotropy, (Na⁺ +K⁺)-ATPase inhibition