Functional Modulation of the Sodium Pump: The Regulatory Proteins "Fixit"
T he Na-K-ATPase is the integral membrane enzyme responsible for the active coupled transport of Na + and K + across the plasma membranes of animal cells. The enzyme is activated by the simultaneous presence of Na + and K + and is specifically inhibited by the plant glycoside ouabain. The generation and maintenance of the electrochemical gradients for Na + and K + requires energy that is derived from the hydrolysis of ATP, which in humans can amount to 25% of the basal metabolic rate. These
... rconnected functions are the basis for its equivalent designation as the Na/K pump or Na-K-ATPase. The Na-K-ATPase is a heterodimer composed of a catalytic D-subunit, which undergoes conformational changes that couple ATP hydrolysis to ion transport, and the E-subunit, which is responsible for maturation, assembly, and membrane targeting of the enzyme. The Na-K-ATPase is a member of Ptype ATPases in which a transfer of the J-phosphate from ATP to an active site in the enzyme is taking place. Other members of this family include the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) and the gastric H-K-ATPase. The ion gradients maintained by the Na-K-ATPase, together with the different permeability of the cell membrane to Na + and K + , form the basis for the resting membrane potential, counteract the Donnan effect (which would otherwise lead to cell lysis) and provide the energy for many co-and countertransport systems. In excitable tissue of nerves and muscles, it reestablishes the ion gradients that are dissipated after depolarization. In transport epithelia of kidney, intestine, and secretory glands, its polarized localization to basolateral membrane compartments provides the driving force for water and salt transport. Thus the Na-K-ATPase is of paramount importance for cell homeostasis and is as such under strict hormonal control, as described in the excellent review by Therien and Blostein (15), where references up to the year 2000 can be found.