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Canrenoate, an aldosterone antagonist, was administered to normal and ouabaintreated Purkinje fibers excised from the hearts of mongrel dogs and perfused with Tyrode's solution at 35–37°C. Intra- and extracellular potentials were recorded with conventional techniques. Potassium canrenoate in concentrations up to 1 × 10−3M or sodium canrenoate in concentrations up to 5 × 10−3M had inconspicuous electrophysiological effects on untreated Purkinje fibers. The duration of the action potential was slightly shortened. Amplitude of resting and action potentials, rate of rise of action potentials, conduction velocity, membrane responsiveness, automaticity, and excitability were not significantly altered by canrenoate. In contrast, potassium canrenoate in concentrations of 1 × 10−4M to 5 × 10−4M produced rapid restoration toward normal of fibers moderately or severely affected by ouabain (10−7M). Resting and action potentials were augmented, rate of rise of action potentials was increased, excitability was restored, and conduction was enhanced. Also ouabain-induced spontaneous rapid firing could be terminated. Twice equimolar doses of KCI were ineffective. The data suggest that canrenoate might be a specific antagonist to the electrophysiological effects of digitalis.

Reversal of Ouabain-Induced Electrophysiological Effects by Potassium Canrenoate in Canine Purkinje Fibers