Dependence of the cardiac uptake of digitalis glycosides on the extracellular calcium concentration in guinea pig isolated hearts.

The purpose of the present study was to investigate, at the myocardial level, the divergent influences of Ca2+ on the action of various cardiotonic steroids. Therefore, the cardiac uptake of 3-H-digitoxin and 3-H-digitoxin was studied in experiments on guinea pig isolated hearts. The following results were obtained: with digitoxin the increase of the extracellular calcium concentration from 0.45 upto 7.2 mM resulted in a concomitant decrease of the myocardial glycoside uptake from about 1.8 nmoles/g wet weight down to about 1.2 nmoles/g wet weight. Similar results were obtained when digoxin uptake was studied under the same conditions: with 0.45 mM Ca2+ about 0.6 nmoles/g wet weight were bound, increasing the calcium concentration upto 7.2 mM lead to a concomitant decrease of the cardiac digoxin uptake down to about 0.45 nmoles/g wet weight. Despite the different physicochemical behaviour of these two drugs and the different amounts of drug present in the hearts the influence of Ca2+ was almost identical if calculated on a relative basis. So far, no experimental based explanation can be given for the above discrepancies. Other possible interpretations are discussed.