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. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Apoptosis. 2015 Sep;20(9):1200–1210. doi: 10.1007/s10495-015-1144-y

Fig. 7.

Fig. 7

Hypothetical mechanisms underlying the distinct impact of cardiotonic steroids (CTS) on survival of cells, expressing the CTS-sensitive (α1S) and the CTS-resistant (α1R) Na+,K+-ATPase subunits. In both cases, saturating levels of CTS strongly increase the [Na+]i/[K+]i ratio. In addition, CTS trigger distinct conformational changes in α1S and α1R isoforms that, in turn, affect their interactions with unknown protein partner(s) I and II. These subsequent signaling events lead to activation of p38 and ERK1/2 MAPK and result in cell death and survival, respectively. ? – steps showing possible additional effects of the transcriptomic changes, which can be directly induced by elevation of the [Na+]i/[K+]i ratio. For more details, see text.