The role of calcium in digitalis toxicity of the sino-atrial node

The role of calcium on digitalis toxicity was studied in the sinus node of the guinea pig. In guinea pig sinus node isolated from the atrium, digoxin (0.5 μM) increased the spontaneous discharge and eventually induced tachyarrhythmia. In contrast to Purkinje fibers, in the presence of digoxin, high [Ca](o) (8.1 mM) markedly increased the SA node rate (and the increase was much larger than in control). Such acceleration was abolished by low [Ca](o) (0.27 mM). Low [Ca](o) (0.27 mM) slowed the digoxin-induced sinus tachyarrhythmia whereas it increased the rate in the absence of digoxin. TTX had little effect on digitalis toxicity whereas manganese markedly reduced digoxin-induced tachyarrhythmia and prevented it altogether if given simultaneously with digoxin. Once the SA node had been stopped by means of acetylcholine administration, ouabain induced DD, V(os) and aftercontractions. A period of fast drive induced overdrive excitation. Therefore, it appears that digitalis causes Ca overload and its manifestations in the SA node as it does in other cardiac tissues. However, the response of the SA node to changes in [Ca](o) is different from that of Purkinje fibers due to the different role of Ca in diastolic depolarization and excitation of the SA node.