Na+/K+-ATPase

Structure of the Enzyme and Mechanism of Action of Digitalis
  • Arnold Schwartz
  • John H. Collins

Abstract

There seems to be no doubt that the Na+/K+-ATPase is the enzyme that represents the machinery of active transport of sodium and potassium across cell membranes. Very early in evolution, critical ion gradients must have been established; movement involving the expenditure of energy across membrane barriers must also have represented an early development, for without this mechanism, important biological processes could not exist. These include nerve excitability, motility, maintenance and possible regulation of cell volume, excretion, and reabsorption, a variety of sodium-dependent or -coupled transport processes, and electrical and mechanical activity of muscle. While an ATP-dependent process for transport was recognized for many years, it was not until the work of J. C. Skou (1957, 1960) that a specific enzyme system was recognized. Among the criteria for recognition of this enzyme is the very potent inhibition of ATP hydrolysis by cardiac glycosides. Thousands of papers have been published using ouabain, a water-soluble glycoside, as a marker for this important enzyme. When we examine the structure of a typical cardiac glycoside, we are struck with its apparent similarity to hormonal steroids. The geometrical configuration, however, is quite different Like the steroids, the glycosides are used in very low concentrations to produce their effects. The primary effect on the intact organism is an increased force of contraction of heart muscle, a discovery made by William Withering more than 200 years ago. This class of drugs is still the most widely used in the treatment of heart failure. The fascination with this drug also arises from its very potent inhibitory effect on Na+/K+-ATPase, so it is not illogical that it is employed as a “chemical tool” to, on the one hand, dissect the mechanism of action of the Na+/K+-ATPase and on the other hand to search for the mechanism of its action on the heart.

Keywords

Hydrolysis Magnesium Carbohydrate Glycine Morphine 

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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Arnold Schwartz
    • 1
  • John H. Collins
    • 1
  1. 1.Department of Pharmacology and Cell BiophysicsUniversity of Cincinnati College of MedicineCincinnatiUSA

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