Influence of extracellular potassium concentration on myocardial uptake and inotropic effect of tritiated digoxin.

Because of conflicting reports on the influence of extracellular potassium concentration ([K]o) on the inotropic action of cardiac glycosides, we compared the effects of varying [K]o (1.5, 4.5, and 7.5mM) on the inotropic action and myocardial concentration of tritiated digoxin (5 X 10~M) using the isolated cat papillary muscle. The time course of the inotropic response to digoxin was significantly altered by [K]o in an inverse manner; the rate of change of the active tension response to digoxin (g/mm • min") was 0.048 + 0.004 with low [K]o, 0.025±0.003 with normal {K]o and 0.014+0.002 with high [K]o. There were no differences, however, in the peak inotropic responses achieved at each [K]o. Muscles were analyzed for H-digoxin content after 45 minutes, and at the time of the peak inotropic response. The relationships found between [K]o and H-digoxin content were similar to those found between l[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]o and the rate of development of the inotropic response to digoxin, changes that may be due to a [K]o induced alteration in myocardial digoxin content.