Respective involvements of high- and low-affinity digitalis receptors in the inotropic response of isolated rat heart to ouabain.
High- and low-affinity digitalis receptors coexist in rat cardiac sarcolemma. In this study, their relative involvement in the inotropic effect of ouabain was evaluated on an isolated Langendorff rat heart preparation working under isovolumic conditions at a low external calcium concentration (0.25 mM). This involvement was estimated according to both the development of the inotropic response to ouabain (10(-8)-10(-4)M) and the time course of the washing out of the biological effect. In each phenomenon considered, and whatever the index of inotropy chosen, the high-affinity digitalis receptor (EC50: 1-2 X 10(-8) M) contributed to 25-40% of the maximal inotropy (evoked by 10(-4) M ouabain). Low-affinity receptors (EC50: 1-2 X 10(-5) M) accounted for 60-75%. These apparent affinities were identical to those previously determined in sarcolemma isolated from rat heart perfused with 0.25 mM Ca2+. The biphasic effect of ouabain was related to both the inhibition of high- and low-sensitivity Na+, K+-ATPase forms and the corresponding number of ouabain-binding sites occupied. These results support the concept that the Na+, K+-ATPase highly sensitive to ouabain as revealed by lowering calcium is the in vivo manifestation of the high-sensitivity inotropic component.
D000818:Animals; D001665:Binding Sites; D008433:Mathematics; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D011955:Receptors, Drug; C027082:digitalis receptor; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase