An intracellularly induced positive inotrophic effect of manganese in guinea-pig ventricular myocardium

1. Manganese ions (0.3-2.4 mmol/l, applied as MnCl₂) produced a concentration-dependent rapid decrease in force of contraction (F_c) of guinea-pig papillary muscles; 0.6 mmol/l diminisched F_c by about 50%. The initial decrease in F_c was followed by a concentration-dependent positive inotropic effect which, within 60-90 min, led to a F_c value of 100% and more above the control (contraction frequency 0.625 Hz). 2. The positive inotropic effect of Mn²⁺ was associated with an increase in the rate of contraction and a marked, concentration-dependent prolongation of the relaxation time (by 80% in the presence of 1.2 mmol/l Mn²⁺). Concomitantly, the duration of the action potential was slightly shortened. 3. The development of the positive inotropic effect of Mn²⁺ depended on the stimulation frequency. The half-time values for the increase in F_c were 27, 11 and 5 min at the frequencies of 0.5, 0.625 and 1 Hz, respectively. 4. After washout of Mn²⁺ (0.6 mmol/l) the negative inotropic effect disappeared rapidly with a half-time of 0.5 min whereas the positive inotropic effect declined slowly (half-time 38 min). 5. It is concluded that, in addition to a negative inotropic effect due to an action on the sarcolemmal membrane, Mn²⁺, following its stimulation-induced uptake, exerts a positive inotropic effect by an intracellular action. Inhibition of sequestration of Ca²⁺ by intracellularly accumulated Mn²⁺ probably plays a role in the positive inotropic effect.