Muscle sodium-potassium ATPase

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

Escalante B, Sessa WC, Falck JR, Yadagiri P, Schwartzman ML (1990) Cytochrome P450-depen-dent arachidonic acid metabolites, 19- and 20-hydroxyeicosatetraenoic acids, enhance sodium-potassium ATPase activity in vascular smooth muscle. J Cardiovasc Pharmacol 16 438-443... 

With active transport, energy is expended to move a substance against its concentration gradient from an area of low concentration to an area of high concentration. This process is used to accumulate a substance on one side of the plasma membrane or the other. The most common example of active transport is the sodium-potassium pump that involves the activity of Na+-K+ ATPase, an intrinsic membrane protein. For each ATP molecule hydrolyzed by Na+-K+ ATPase, this pump moves three Na+ ions out of the cell and two K+ ions into it. As will be discussed further in the next chapter, the activity of this pump contributes to the difference in composition of the extracellular and intracellular fluids necessary for nerve and muscle cells to function. 

Cantley, L.C., Jr., L. Josephson, R. Warner, M. Yanagisawa, C. Lechene, and G. Guidotti. 1977. Vanadate is a potent (sodium, potassium ion)-dependent ATPase inhibitor found in ATP derived from muscle. J. Biol. Chem. 252 7421-3. 

Natriuretic hormone inhibits sodium and potassium ATPase and thus interferes with sodium transport across ceU membranes. Inherited defects in the kidney s ability to eliminate sodium can cause an increased blood volume. A compensatory increase in the concentration of circulating natriuretic hormone theoretically could increase urinary excretion of sodium and water. However, this same hormone is also thought to block the active transport of sodium out of arteriolar smooth muscle cells. The increased intracellular concentration of sodium ultimately would increase vascular tone and BP. 

Digitalis glycosides block the activity of sodium-potassium adenosinetriphosphatase (ATPase). This inhibits the recovery of the cardiac myocyte from depolarization in a dose-dependent manner. This, in turn, results in a buildup of sodium within the cell and potassium outside of the cell, with successive depolarizations. The increase in intracellular sodium inhibits the membrane sodium-calcium transporter, allowing accumulation of calcium within the cell. The transporter may eventually reverse, and intracellular sodium is exchanged for extracellular calcium (see Figure). The resulting increase in intracellular calcium mediates an increase in the force of contraction of the cardiac muscle. 

The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiological changes is still not completely known despite years of active investigation. Several mechanisms have been proposed, but the most widely accepted mechanism involves the ability of cardiac glycosides to inhibit the membrane-bound Na /K -adenosine triphosphatase (Na /K -ATPase) pump responsible for sodium/potassium exchange. To understand better the correlation between the pump and the mechanism of action of cardiac glycosides on the heart muscle contraction, one has to consider the sequence of events associated with cardiac action potential that ultimately leads to muscular contraction. The process of membrane depolarization/repolarization is controlled mainly by the movement of the three ions, Na", K", Ca ", in and out of the cell. 

The question for the nutritionist and clinician is Which Mg-dependent function is most sensitive to depletion of the body s magnesium and to hypomagnesemia The answer is probably ion transport systems, such as the calcium pump and Np,K-ATPase. The impaired activity of these ion pumps is likely to be responsible for the neuromuscular problems that present with an Mg deficiency. The defects would involve a difficulty in maintaining the normal movements of calcium, sodium, and potassium ions required for nerve conduction and muscle contraction,... 

Potassium is accumulated within cells by the action of the Na. K -ATPase (sodium pump) in which it participates in exchange for sodium that is extruded from the cell during potassium uptake [10]. Potassium has a major function as a carrier of charge within cells [1]. It is extremely mobile and therefore if it is allowed to pass through membranes it may be used to regulate potentials across cells, especially excitable cells such as muscle and nerve [16]. The regulation of such metal ion flows, especially of potassium and sodium, is crucial to life and is most clearly exemplified by the ionic movements that occur in nerve cells during excitation and transmission of the action potential [17]. 

An ATPase has been found in association with cell membranes. The enzyme is stimulated by sodium and inhibited by cardiac glycosides (ouabain and digitalis). If potassium is present, the stimulation by sodium is enhanced. The enzyme originally described in crab nerve and erythrocyte ghost was later found in a number of tissues— kidney, ciliary body, brain, giant axon, ascites cell, skin cell, lens, leukocyte, and skeletal and heart muscle. 

The activity of ion transport systems, such as sodium- and potassium-activated adenosine triphosphatase, has been studied In vivo by the use of rubidium-87 MRS. This has been possible because rubidium has been shown to substitute for potassium in a number of transmembrane transport systems, accumulating in the intracellular space. Standard in vitro methods of determining Na+/K+-ATPase activity, which also use rubidium, give highly variable measurements and in some cases contradictory results. Many of these problems appear to have been overcome by the use of in vivo Rb MRS, especially when sequential measurements are required. In a longitudinal study of spontaneously hypertensive rats, Rb MRS showed that skeletal muscle rubidium rose at a faster rate in hypertensive rats than in control animals, which is consistent with a marked increase in Na+/K+-ATPase activity. This type of experiment emphasizes the value of in vivo MRS since rubidium kinetics can be determined sequentially on the same animal, minimizing inter/intra-subject variability as well as the number of animals required in the study. 

Excess of potassium in the body dam2iges the tissues of the body and muscles are contracted violently. It also increases ATPase and kinase activity with the loss of sodium ions. Hyperkalemia is foimd in patients suffering from (i) Addison s disease (ii) diabetes melitus (iii) renal failure (iv) severe dehydration. 

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