On the cooperativity of ouabain-binding to intact myocardium |
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Authors: | S Herzig H Lüllmann K Mohr |
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Affiliation: | Department of Pharmacology, University of Kiel, Hospitalstrasse 4-6, 2300 Kiel 1, FRG |
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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. |
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Keywords: | Cooperativity Ouabain-binding Na/K-ATPase Intact myocardium |
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