Interactions of cardiac glycosides with cultured cardiac cells. II. Biochemical and electron microscopic studies on the effects of ouabain on muscle and non-muscle cells.

Electron microscopic and biochemical studies revealed a salient difference in the response to toxic doses of ouabain by cultured cardiac muscle and non-muscle cells from neonatal rats. Progressive cellular injury in myocytes incubated with 1 . 10(-4)--1 . 10(-3) M ouabain ultimately leads to swelling and necrosis. The morphological damage in myocytes was accompanied by a drastic decrease in 14CO2 formation from 14C-labeled stearate or acetate but not glucose. Neither morphological nor biochemical impairments were observed in non-muscle cells. The interaction between ouabain and the cultured cells, using therapeutic doses of ouabain (i.e., less than 1 . 10(-7) M), was characterized. Two binding sites were described in both classes of cells, one site is a saturable K+-sensitive site whereas the other is non-saturable and K+-insensitive. The complexes formed between the sarcolemma receptor(s) and ouabain, at low concentrations of the drug (e.g., 7.52 . 10(-9) M), had Kd values of 8.9 . 10(-8) and 2.3 . 10(-8) M for muscle and non-muscle cells, respectively. The formation and dissociation of the complexes were affected by temperature and potassium ions.