Na+, K(+)-ATPase and Na+/Ca2+ exchange isoforms: physiological and physiopathological relevance

Different isoforms of the (Na+ + K+)-ATPase are expressed in different cell types in which they contribute to specialized properties. Their biochemistry and physiology are complex. These isozymes vary in their sensitivity to cardiac glycosides and to intracellular Na+ and Ca2+ concentrations. Their functional expression at the membrane level in the different parts of kidney, heart, and brain varies with species and during ontogenesis. In rat heart, at birth and postpartum, there are quantitative and qualitative changes in the expression of the (Na+ + K+)-ATPase and Na+/Ca2+ exchange isoforms. The (Na+ + K+)-ATPase isozymes react differently to hormonal regulation and to physiopathological alterations, i.e., cardiac ischemia and cardiac hypertrophy. Considering the diversity of the (Na+ + K+)-ATPase isoforms and their numerous regulations, what could be the targets of endogenous (Na+ + K+)-ATPase inhibitors?