The interaction of ouabain and salicylate on sheep cardiac muscle.

Abstract

The action potential duration in sheep ventricular fibers is rapidly diminished on exposure to 10-6 M ouabain. If 10-20 mM sodium salicylate is added to the ouabain solution, glycoside-induced shortening is prevented and a substantial increase in duration occurs. Sodium salicylate reverses the shortening effect of ouabain if applied after the glycoside is allowed to act alone. Sodium salicylate alone produces a smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. Other surface charge agents were compared with salicylate: aminonaphthalene sulfonate, sodium dodecylsulfate and salicylamide. These were unable to counter the actions of ouabain at the concentrations used. Since they produced no changes in excitability they probably did not bind significantly to the cell membrane. In Purkinje fibers the reversal potential for the pacemaker current, iK2, is initially shifted in a negative direction in the presence of 10-6 M ouabain and 10 mM salicylate instead of the positive shift expected with ouabain alone at this concentration. In guinea pig ventricle salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain reduce the action potential duration but this effect takes several hours to reverse. The effects of salicylate and ouabain applied together are readily reversible. The mechaniam of these effects may depend on the ability of a surface negative charge agent like salicylate to increase the surface K+ concentration at the membrane and protect the Na-K pump from inhibition by large doses of ouabain.