Diverse biological responses to different cardiotonic steroids Moran Dvela, Haim Rosen, Tomer Feldmann, Maoz Nesher, David Lichtstein  Pathophysiology  Volume 14, Issue 3, Pages 159-166 (December 2007) DOI: 10.1016/j.pathophys.2007.09.011 Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Structure of cardenolides (ouabain and digoxin) and bufadienolides (bufalin and marinobufagenin). Pathophysiology 2007 14, 159-166DOI: (10.1016/j.pathophys.2007.09.011) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Inhibition of digoxin-induced changes in membrane traffic by ouabain. NT2 cells were grown on glass cover slips for 24h. The medium was then replaced with medium containing digoxin, ouabain or a mixture of the two steroids. Following 20min incubation, the medium was removed and the cells were incubated for 5min in PBS containing FM1-43. The reagent was then removed and the cells were washed twice with PBS, and incubated for an additional 4h in the presence of the steroids. Images were obtained using a fluorescence microscope. (A–C) Merged images of the phase contrast and fluorescence signals. Quantification of the ouabain effect on digoxin-and bufalin-induced changes in FM1-43 accumulation is depicted in (D) and (E), respectively. Reproduced from Fig. 2 of Ref. [52] with permission of Am. J. Physiol. Pathophysiology 2007 14, 159-166DOI: (10.1016/j.pathophys.2007.09.011) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 Multiple pathways for biological responses of CS. CS can interact with different receptor complexes of the Na+, K+-ATPase, resulting in inhibition of ion transport or activation of signal transduction mechanism, resulting in a diversity of biological responses. Pathophysiology 2007 14, 159-166DOI: (10.1016/j.pathophys.2007.09.011) Copyright © 2007 Elsevier Ireland Ltd Terms and Conditions