Abstract

Using a photoelectric recording system developed in our laboratory, we have examined the actions of digoxin, dihydrodigoxin and their covalently bound albumin conjugates on cultured heart cells. Our results indicate that albumin-linked glycosides, shown to be free of unbound drug by gas-liquid chromatography, elicited dose-related increases in contraction amplitude and contraction rate from the cells. Data obtained from double isotope labeling experiments suggested that the albumin-digoxin complex did not enter the cell interior. Sustained high potassium levels prevented the increase in cellular contraction rate without altering the increase in contraction amplitude or the cellular uptake of the glycosides. The albumin-linked glycosides also specifically inhibited a particulate (Na + K)-adenosine triphosphatase from rat heart. These data support the hypothesis that digoxin exerts its pharmacological actions on the heart by means of a surface interaction on the cell membrane.