Mechanism of the positive staircase ; relation to the mechanism of the positive inotropic action of digitalis

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It is generally accepted that the mechanism of the positive intropic effect of digitalis is mediated through an increase in intracellular Na concentrations. The objective of this project was to betermine whether an increase in developed tension caused by an increase in stimulation frequency has the common mechanism for digitalis, described above. The force of contraction stury and the ^<86>Rb uptake study were performed in the first year(1987), and the (^3H)ouabain binding study was performed in the 2nd year(final year). Experimental results were summarized as follows.1. Force of contraction study : (1) A step-wise increase in the frequency of stimulation caused a nigative staircase(NS) in left atrial preparations of the rat heart and ventricular preparations of the carp heart. Ryanodine converted the NS to a positive staircase(PS), however, this agent did not alter a concentration depenfent positive intropic effect of ouabain. (2) In left atrial preparations of rabbit and guinea pig h … More earts, the PS was observed. Nifedipine, verapamil or diltiazem converted the PS to the NS. However, these Ca antagonits did not affectthe concentration dependent positive inotropic effect of strophanthidin. (3) ventricular preparations of the carp heart has the PS. However, the sensitivity of the carp heart to the positive inotropic effect of strophanthidin was higher compared to that of the guinea pig left atrial preparations which have the PS. (4) ventricullar preparations of neonatal and abult rat hearts have the PS and NS, respectively, howrver, sensitivity to the positive inotropic effect of low dose ouabain was higher in the adult rat.2. ^<86>Rb uptake srudy : in left atrial preparations of the guinea pig heart,^<86>Rb uptake was increased by electrical stimulation. While, in left atrial preparations of the rat heart, a resting ^<86>Rb uptake was higher than in the guinea pig heart, and the stimulation frequency dependent uptake was lower.3. (^3H)ouabain binding study : affinity of the binding sites for (^3H)ouabain was higher in carp ventricular muscles compared to that of guinea pig atrial muscles. These results indicate a clear dissociation between the force staircase and the sensitivity of heart muscle to the positive inotropic effect of digitalis. Organic Ca antagonists or ryanodine-sensitive Ca pools may play an important role for the staircase. Less