The interaction of ouabain and salicylate on sheep cardiac muscle.
1. The action potential duration in sheep ventricular fibres is rapidly diminished on exposure to 10(-6) M-ouabain. However, if 10--20 mM-sodium salicylate is added to the ouabain solution, glycoside-induced shortening is prevented, and a substantial increase in duration then occurs. Sodium salicylate also reverses the shortening effect of ouabain if applied after the glycoside has been allowed to act alone. 2. Sodium salicylate alone produces a much smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. 3. Three other surface charge agents have been compared with salicylate: aminonaphthalene sulphonate, sodium dodecylsulphate and salicylamide, were unable to counter the actions of ouabain at the concentrations used. Since they also produced no changes in excitability it is likely that they did not bind significantly to the cell membrane. 4. In Purkinje fibres 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. 5. In guinea-pig ventricle, salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain also reduce the action potential duration but this effect takes several hours to reverse. By contrast, the effects of salicylate and ouabain applied together are readily reversible. 6. It is suggested that the mechanism 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 so protect the sodium-potassium pump from inhibition by large doses of ouabain.
D000200:Action Potentials / Q000187:drug effects; D000817:Anilino Naphthalenesulfonates / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology*; D012756:Sheep; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D016276:Ventricular Function
D000817:Anilino Naphthalenesulfonates; D012457:Salicylamides; D012459:Salicylates; D012967:Sodium Dodecyl Sulfate; D010042:Ouabain; D011188:Potassium