Modification by ouabain of the electrical and mechanical effects of acetylcholine in isolated rabbit atria

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Abstract
Summary: Left atrial preparations isolated from rabbits were stimulated electrically at frequencies between 6 and 240/min. Tension‐frequency curves were obtained from control preparations and preparations treated with ouabain and acetylcholine. Transmembrane potentials were recorded from single cells of the left atrium stimulated at different frequencies. The tension‐frequency curve was moved downwards by acetylcholine (10−6 g/ml). Ouabain (10−6 g/ml) caused characteristic alterations in the tension‐frequency relationship, enhancing the contractile tension at low but not high frequencies. The negative inotropic effect of acetylcholine was reduced by treatment with ouabain. Action potential durations were significantly influenced by alterations in frequency of contraction. The 10% duration increased with frequency within the range between 6 and 60/min but decreased at frequencies higher than 120/min. The 50% duration increased with frequency between 6 and 120/min but decreased at frequencies higher than 180/min. The dependence of the 50% duration upon frequency paralleled that of contractile tension. The 90% duration, the overshoot and the resting potential were not affected by frequency of contraction. Acetylcholine (10−6 g/ml) shifted the 10%, 50% and 90% duration‐frequency curves downwards, but did not significantly alter the overshoot and the resting potential. Ouabain (10−6 g/ml) shifted the duration‐frequency curves downwards and also reduced the size of the overshoot and the resting potential. Treatment of atrial preparations with 10−6 g/ml ouabain potentiated the membrane effects of acetylcholine. The inhibition by ouabain of the negative inotropic effect of acetylcholine did not appear to be due to antagonism at the receptor level, but to interference with the mechanisms responsible for the mechanical events.