INFLUENCE OF MANGANESE-IONS ON POSITIVE INOTROPIC EFFECT OF ADRENALINE, THEOPHYLLINE, AND DIGITOXIGENIN IN ISOLATED GUINEA-PIG AURICLES

The influence of bivalent manganese ions (Mn++) on the positive inotropic effect of adrenaline, theophylline, and digitoxigenin was studied in isolated, electrically driven left guinea-pig auricles in phosphate-free Tyrode's solutions with different extracellular calcium concentrations ([Ca]e; 0.45; 1.8; 7.2 mM). Mn++ (0.1-50 mM) exerted a dose-dependent negative inotropic effect which was dependent on [Ca]e: Raising [Ca]e decreased the inhibitory action of Mn++. The negative inotropic effect of Mn++ was exclusively due to a decrease in the rate of tension development; the time to peak tension and the duration of contraction remained unchanged. In a solution containing 0.45 mM Ca, pretreatment with 0.1 mM Mn+ significantly diminished the positive inotropic effect of adrenaline (10-9-10-5 g/ml) and theophylline (5×10-6-10-3 g/ml), but did not influence the effect of digitoxigenin (2×10-7-2×10-6 g/ml). The depression of the positive inotropic effect of adrenaline and theophylline with higher concentrations of Mn+ (0.35-2.25 mM, producing a negative inotropic effect of about 50%) was influenced by the [Ca]e. The effect of Mn+ was most evident at 0.45 mM Ca, less pronounced (but significant) at 1.8 mM Ca and was not observed at 7.2 mM Ca. With the same concentrations of Mn+, however, the positive inotropic effect of digitoxigenin was only slightly decreased at 0.45 mM Ca, was not changed at 1.8 mM Ca and was increased at 7.2 mM Ca. As Mn+ selectively blocks the inward movement of Ca ions across the membrane of the myocardial cell during depolarisation, it is tentatively concluded from these experiments that the positive inotropic effect of adrenaline and theophylline may be due at least partially to an increase of the Ca influx during the excitation process, whereas the positive inotropic effect of digitoxigenin seems to be independent of this mechanism. © 1969 Springer-Verlag.