Quabain: Temporal relationship between the inotropic effect and the in vitro binding to,and dissociation from, (Na++K+)-activated ATPase

Summary The time course of the inotropic response to ouabain in Langendorff preparations was compared with that of the in vitro ATP-dependent (³H)-ouabain binding to cardiac (Na⁺+K⁺)-activated ATPase preparations, and subsequent dissociation, to determine the temporal relationship between the inotropic response and (Na⁺+K⁺)-activated ATPase inhibition.Species differences were minimal either in the onset of inotropic response or the (³H)-ouabain binding. The rates of both loss of the inotropic response to ouabain during washout and the dissociation of the ouabain-enzyme complex, however, were rapid in guinea pig and rabbit (relatively ouabain-insensitive species) and slow in cat and dog (ouabain-sensitive species). The half-time of the loss of the inotropic response was similar to the half-time of the dissociation of the ouabain-enzyme complex in each species.Since ATP-dependent binding of cardiac glycosides has been related to enzyme inhibition, it was concluded that the time course of the inotropic response to ouabain parallels the time course of (Na⁺+K⁺)-activated ATPase inhibition, and that the dissociation of ouabain from the enzyme may terminate the inotropic response.A part of this study was presented at the Fifth Annual Meeting of the International Study Group for Research in Cardiac Metabolism, Winnipeg, Manitoba, June, 1972.