Influence of Extracellular Potassium Concentration on Myocardial Uptake and Inotropic Effect of Tritiated Digoxin

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Abstract
Because of conflicting reports on the influence of extracellular potassium concentration ([K] 0 ) on the inotropic action of cardiac glycosides, we compared the effects of varying [K] 0 (1.5, 4.5, and 7.5m M ) on the inotropic action and myocardial concentration of tritiated digoxin (5 x 10 -7 M ) using the isolated cat papillary muscle. The time course of the inotropic response to digoxin was significantly altered by [K] 0 in an inverse manner; the rate of change of the active tension response to digoxin (g/mm 2 · min -1 ) was 0.048±0.004 with low [K] 0 , 0.025±0.003 with normal [K] 0 and 0.014±0.002 with high [K] 0 . There were no differences, however, in the peak inotropic responses achieved at each [K] 0 . Muscles were analyzed for 3 H-digoxin content after 45 minutes, and at the time of the peak inotropic response. The relationships found between [K] 0 and 3 H-digoxin content were similar to those found between [K] 0 and active tension. Moreover, a significant positive correlation between digoxin content and the increment in active tension was observed. Thus, an inverse relationship exists between [K] 0 and the rate of development of the inotropic response to digoxin, changes that may be due to a [K] 0 induced alteration in myocardial digoxin content.