title: On the cooperativity of ouabain-binding to intact myocardium.
abstract: A theoretical concept is presented which proposes that binding of ouabain to intact myocardium should be positive cooperative. It is based on the assumption that the myocardial Na/K-ATPases expose the ouabain-binding site only at a particular conformation adopted during a turnover cycle. The turnover rate and thus the ouabain-binding properties are regulated by the cytosolic Na-ion-concentration Nai. Any occupation of cellular Na/K-ATPases should affect the ouabain-binding properties of the unoccupied Na/K-ATPases, because their turnover rate is increased via an elevated Nai. A computer model which takes into account the interrelationships of the Na/K-ATPases both with Nai and with the ouabain-concentration predicts that ouabain-binding should proceed in a concentration-proportional fashion as long as the Na-load can be counterbalanced by non-occupied Na/K-ATPase molecules. The concentration-proportional binding reflects a positive cooperativity. Experimental results reveal that (3H)ouabain-binding to Na/K-ATPase of electrically stimulated guinea-pig left atria was in fact concentration-proportional under certain experimental conditions. The biological significance of the proposed concept remains to be elucidated.
mesh_terms: D000818:Animals; D001665:Binding Sites; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism*; D011487:Protein Conformation; D011955:Receptors, Drug / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D011955:Receptors, Drug; C028996:cardiac glycoside receptors; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase