Positive inotropic action of digoxigenin and sodium pump inhibition: effects of enhanced sodium influx.
A possibility that intracellular Na+ ions available to Na+,K+-adenosine triphosphatase influence the action of digoxigenin to cause sodium-pump inhibition and a positive inotropic effect was examined with isolated left atria of guinea-pig hearts. The positive inotropic action of digoxigenin developed more rapidly when atria were stimulated at 3 Hz than at 1.5 Hz. The rate of development of the positive inotropic action was dependent on the frequency of membrane depolarizations rather than on contractions. Monensin, a known Na+ ionophore, enhanced the rate of development of the positive inotropic action of digoxigenin. Sodium pump activity, as estimated from ouabain-sensitive 86Rb uptake, was inhibited by digoxigenin in a concentration-dependent manner in quiescent atria. The inhibition was enhanced by electrical stimulation which shifted the concentration-inhibition curves to the left. The sensitivity of the sodium pump for digoxigenin was also affected by membrane depolarizations, suggesting a role for intracellular Na+. These data indicate that similar to the cardiac glycosides, the interaction of the aglycone with Na+,K+-adenosine triphosphatase is essential for the development of the positive inotropic action of this agent.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004076:Digoxigenin / Q000494:pharmacology*; D004077:Digoxin / Q000031:analogs & derivatives*; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*
D010042:Ouabain; D004077:Digoxin; D008985:Monensin; D012964:Sodium; D004076:Digoxigenin