FIGURE 3.

Model showing basolateral NKA ionic and signaling pathways. Ionic pathway involves: (i) high dose cardiotonic steroids inhibiting NKA activity, (ii) increased intracellular Na⁺ concentration, (iii) decreased intracellular K⁺ concentration, and (iv) increased intracellular Ca²⁺ concentration inducing genomic effects in the nucleus. Signaling pathway involves: (i) low dose cardiotonic steroid binding, (ii) release of Src, (iii) activation of EGFR, and (iv) signaling cascade activation of mitogen-activated protein kinase kinase (MEK/ERK), ROS generation, PLC/PKC activation, and PI3K/Akt activation.