Carp (Cyprinus carpio) heart has a high sensitivity to the positive inotropic effect of strophanthidin despite negative force-frequency relationships.
1. The relationship between response of the heart to increased stimulation frequency and digitalis sensitivity was examined comparing the positive inotropic effect of strophanthidin and [3H]ouabain binding to sarcolemmal Na+, K+-activated adenosine triphosphatase (Na+, K+-ATPase) in carp heart, which showed a negative force-frequency relationship, and in guinea-pig heart, which has a positive relationship. 2. In ventricular muscle preparations isolated from carp heart, strophanthidin increased developed tension with a half-maximal effect observed at 0.31 microM, indicating a relatively high digitalis sensitivity of this preparation. 3. The positive inotropic effect was not altered by concentrations of propranolol sufficient to block beta-adrenergic receptors. 4. Specific binding of [3H]ouabain to homogenates obtained from ventricular muscle of carp heart showed a single class of binding sites with a Kd value of 26 nM. 5. Potency of strophanthidin to produce the positive inotropic effect and affinity of the binding sites for [3H]ouabain were both higher in carp heart compared to those in guinea-pig heart. 6. These results demonstrate a clear dissociation between the force-frequency relationship and the sensitivity of heart muscle to the positive inotropic effect of cardiotonic steroids. 7. The latter is primarily determined by affinity of sarcolemmal Na+, K+-ATPase for the cardiotonic steroids.
Temma
K
K
Department of Veterinary Pharmacology, Kitasato University, School of Veterinary Medicine and Animal Sciences, Aomori, Japan.
Nagatomi
H
H
Hirano
H
H
Kitazawa
T
T
Kondo
H
H
D000818:Animals; D002347:Carps / Q000502:physiology*; D003530:Cyprinidae / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology*
D010042:Ouabain; D013327:Strophanthidin; D011433:Propranolol; D000254:Sodium-Potassium-Exchanging ATPase