Figure 1.

Diagram showing the various effects as well as the different pathways activated by ouabain in ADPKD cells. Ouabain induced and NKA mediated signaling controls ADPKD cell proliferation via the Src-MEK-ERK pathway and cell death via stimulating the intrinsic apoptotic pathway. This effect of ouabain creates a disbalance that favors cell growth, one of the hallmarks of ADPKD cystogenesis. In addition, ouabain stimulates the cAMP dependent secretion of Cl⁻ in the cells by activating the CFTR. This, along with a small reduction in NKA function that lessens Na⁺ reabsorption at the basolateral membrane of the cells, favors epithelial secretion over reabsorption, which helps maintain cyst growth. Also, ouabain induces cell de-differentiation and changes in the expression of adhesion proteins in ADPKD cells, via intracellular pathways that are not yet well characterized. O, ouabain, (α and β) subunits of the Na-K-ATPase. See the text for additional definitions.