MODIFICATION BY SODIUM AND CALCIUM OF THE CARDIOTOXICITY INDUCED BY OUABAIN

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

The effects of ouabain (5 x 10^-8-10^-6 g/ml) on the frequency and force of contraction and on the transmembrane potentials of sinoatrial (S-A) nodal pacemaker cells from rabbits were tested in the presence of various concentrations of Na and Ca. Responses to the electrical stimulation of the right vagus nerve and to the application of acetylcholine (5 x 10^-8-10^-6 g/ml) were observed under the several experimental conditions. The rate of onset of toxicity to ouabain (tachysystole and/or irregularities of beat, depression of contractile force, loss of responsiveness to vagal stimulation and depression of S-A nodal membrane potential) was a direct function of [Na]₀ and [Ca]₀. Low [Na]₀ delayed the onset of toxicity but did not antagonize an established toxicity. In all solutions except that of the lowest [Na]₀ the negative chronotropic response to vagal stimulation was abolished by 10^-6 g/ml of ouabain, although the membranal response was preserved. Except in solutions of the lowest [Na]₀, the administration of ouabain (10^-6 g/ml) augmented the sensitivity of the chronotropic mechanism to acetylcholine, decreased the diastolic and systolic membrane potentials of pacemaker cells and depressed the amplitude, rate of rise and course of diastolic depolarization of pacemaker action potentials. It was concluded that the rate of onset of toxicity to ouabain is directly dependent upon the magnitude of the systolic entry of Na, but is independent of the ratio of the external concentrations of Ca and Na.