Comparison of the Na+ Pump and the Ouabain-Resistant K+ Transport System with Other Metal Ion Transport ATPases
Digitalis has long been of medical importance and was mentioned in herbal treatment as early as 1250 (Schery, 1972). This drug entered into accepted medical practice in 1785 following the experimental observations of William Withering (Withering, 1785). Today it is commonly used as a cardiac drug to strengthen heart muscle contraction. In the 1950s the receptor for this drug was shown to be the plasma membrane ATPase, which actively pumps Na+ out of the cell and K+ into the cell to maintain cytoplasmic ion concentrations (Skou, 1965). The ability of ouabain, a member of the digitalis family of cardiac glycosides, to inhibit the Na+-K+ ATPase has been widely used to characterize this important enzyme. Recently, a gene was cloned that, when transfected into green monkey fibroblasts, rescued cells from ouabain toxicity (Levenson, 1984). Characterization of the resistant cells indicated the presence of a new ouabain-resistant potassium transport system with characteristics similar to but distinct from the native Na+-K+ ATPase (English et al., 1985a,b). In this chapter we discuss some of the structural and kinetic properties of the Na+-K+ ATPase and a family of related cation transport systems. The nature of the transport system induced by the ouabain resistance gene is discussed in relation to this family of proteins.
KeywordsSarcoplasmic Reticulum Catalytic Subunit Cardiac Glycoside Adenosine Triphosphatase Proteolytic Site
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