Cardiac Glycoside Effects on Rat Skeletal Muscle Potentials and Electrolytes

Abstract

Summary

The effect of cardiac glycosides on rat skeletal muscle intracellular action potenials was studied and correlated with changes in serum and muscle electrolytes and water. In the early minutes after subcutaneous administration of ouabain, 25-200 μg, there was a significant shortening of depolarization and repolarization times. After 15-min repolarization lengthened and after 50 min depolarization also becomes prolonged. The early phase of shortening is more easily demonstrated with 25-50 μg doses, and the latter prolongation of the action potential is more marked and consistent with the larger doses.

There is also a biphasic action on muscle water content. This is apparently an increase in intracellular water as no change was seen in inulin space. The time relationship to this effect is unrelated to the time of changes in action potentials. Muscle water was increased for the first hour after injection of ouabain, returned to normal 1 to 2 hr after huge doses of ouabain, 400-600 μg, and was decreased 5 hr after the last of 3 doses of digitoxin over a 24-hr period. Muscle sodium increased significantly and progressively from 15 to 120 min after ouabain and was normal 5 hr after 3 doses of digitoxin. Muscle potassium was decreased after 15 min and became progressively lower over the next 105 min. It was also low 5 hr after 3 doses of digitoxin. Serum and muscle electrolyte and water changes are not demonstrable during the phase of shortening of the stimulated action potential. Prolongation of the action potential correlates in time only with diminution of muscle potassium content. Shortening of the action potential is thought to represent the therapeutic effect of cardiac glycosides, prolongation the toxic effect. Possible correlations with increased active sodium transport and with inhibition of Na and K dependent ATPase are discussed.