The effect of harmine on the action potential of the guinea-pig atrial muscle depends on the external calcium concentration.

1 The influence of the external calcium concentration on the effect of harmine 2 x 10(-5) M upon the guinea-pig atrial muscle was analysed. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30 degrees C. 2 In preparations superfused with 1.35 mM Ca2+-Tyrode solution and driven at 60/min (1 Hz) harmine depressed the amplitude of the action potential (AP) and the maximum velocity of the upstroke (dV/dt). The resting potential was not affected. Harmine depressed similarly the dV/dt of fibres superfused with 2.7 mM Ca2+-Tyrode solution but the AP was slightly enhanced. 3 Harmine diminished both the AP and the dV/dt of fibres superfused with 2.7 mM Ca2+-Tyrode solution and driven at a fast rate (180/min, 3 Hz). Increased external calcium concentration (5.4 mM) annulled the depressant effect on Ap while the action on dV/dt persisted. 4 It is concluded that the effect of harmine on the Ap depends on the external calcium concentration. Increase [Ca2+]o reverses the depressant effect of harmine because it annuls the effect of the drug on the slow component of the upstroke. The action on the initial fast component of the rising phase of the action potential persists.