Sodium-potassium activated ATPase

OUABAIN A chemical of botanic origin that inhibits sodium-potassium-activated ATPase in cell membranes, thereby being toxic to the cell the selection of mutants that are resistant to the toxic effects of ouabain provides the basis of a mutation-detection system in mammalian cells. 

Removal of norepinephrine Norepinephrine may (1) diffuse out of the synaptic space and enter the general circulation, (2) be metabolized to O-methylated derivatives by post-synaptic cell membrane-associated catechol O-methyltransferase (COMT) in the synaptic space, or (3) be recaptured by an uptake system that pulls the norepinephrine back into the neuron. The uptake by the neuronal membrane involves a sodium-potassium activated ATPase that can be inhibited by tricyclic antidepressants such as imipramine (see p. 119), or by cocaine (see Figure 6.3). 

Primary active transport systems that have been studied include the sodium-b potassium pump [25,26] (which is the sodium + potassium-activated ATPase) and the calcium ATPase [27] and include also the ATP synthesising proton pumps of mitochondria [18,28]. 

The absorption of thiamin is impaired in alcoholics, leading to thiamin deficiency (Section 6.4.4). In vitro, tissue preparations show normal uptake of the vitamin into the mucosal cells in the presence of ethanol, but impaired transport to the serosal compartment. The sodium-potassium-dependent ATPase of the basolateral membrane responsible for the active efQux of thiamin into the serosal fluid is inhibited by ethanol (Hoyumpa et al., 1977). 

Previous work, which has not been revisited, showed that sulfatides are necessary for the optimal function of enzymes such as sodium-potassium-dependent ATPase, and the sulfatide content seems to be directly related to the activity of the enzyme (Karlsson et al., 1974). Sulfatides may also be involved in the functioning of certain opiate receptors (Craves et al., 1980) and in chloride transport systems (Zalc et al., 1978). Implantation in the spinal cord of a hybridoma secreting specific antisulfatide antibodies has been shown to cause demyelination of the CNS in the rat (Rosenbluth et al., 2003). Antisulfatide antibodies have been found in HIV... 

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. 

Among the requirements for enzyme activity are ATP, Mg, Na", and lipids. The requirement for ATP is not absolute. The hydrolysis of ITP, GTP, and CTP can replace that of ATP, but these nucleotides are much less effective than ATP. The hydrolysis of UTP is ineffective in the sodium-potassium—dependent ATPase (Na K ATPase). 

Na+/K+-ATPase sodium pump Sodium- and potassium-activated adenosine 5 -triphosphatase EC 3.6.1.37. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

A well-known example of active transport is the sodium-potassium pump that maintains the imbalance of Na and ions across cytoplasmic membranes. Flere, the movement of ions is coupled to the hydrolysis of ATP to ADP and phosphate by the ATPase enzyme, liberating three Na+ out of the cell and pumping in two K [21-23]. Bacteria, mitochondria, and chloroplasts have a similar ion-driven uptake mechanism, but it works in reverse. Instead of ATP hydrolysis driving ion transport, H gradients across the membranes generate the synthesis of ATP from ADP and phosphate [24-27]. 

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. 

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. 

Amiloride and triamterene-Am or 6e and triamterene not only inhibit sodium reabsorption induced by aldosterone, but they also inhibit basal sodium reabsorption. They are not aldosterone antagonists, but act directly on the renal distal tubule, cortical collecting tubule and collecting duct. They induce a reversal of polarity of the transtubular electrical-potential difference and inhibit active transport of sodium and potassium. Amiloride may inhibit sodium, potassium-ATPase. 

Parenteral /32-agonists such as albuterol (salbuta-mol) increase the activity of the membrane sodium-potassium ATPase, and so increase potassium entry into cells. Nebulized or infused albuterol (salbutamol) significantly lowers serum potassium concentration over 5 hours. A suitable initial dose of nebulized albuterol is 5 mg in adults. It can provoke tremor and tachyarrhythmia, and it is desirable to monitor cardiac rhythm during nebulization. The combination of nebulized albuterol (salbutamol) with infusion of insulin + glucose is more effective than the infusion alone. 

Inorganic ions, such as sodium and potassium, move through the cell membrane by active transport. Unlike diffusion, energy is required for active transport as the chemical is moving from a lower concentration to a higher one. One example is the sodium-potassium ATPase pump, which transports sodium [Na ] ions out of the cell and potassium [K ] into the cell. 

This must obviously be the opposite of passive transport. Active transport does require energy, usually in the form of the consumption of ATP or GTP, because the molecules are moving against the concentration gradient from an area of lower concentration to an area of higher concentration. The most well known active transport system is the Sodium-Potassium-ATPase Pump (Na" "- K+ZATPase) which maintains an imbalance of sodium and potassium ions inside and outside the membrane, respectively. See Figure 3. 

Sodium-Potassium ATPase Pump An Active Transport System... 

One example of molecular transport requiring energy is the reuptake of neurotransmitter into its presynaptic neuron, as already mentioned above. In this case, the energy comes from linkage to an enzyme known as sodium-potassium ATPase (Fig. 2—9). An active transport pump is the term for this type of organization of two neurotransmitters, namely a transport carrier and an energy-providing system, which function as a team to accomplish transport of a molecule into the cell (Fig. 2—11). 

Cardiac glycosides cause a positive inotropic effect which means an increase of the cardiac beat volume by enhanced contraction ability. The reason for this is supposed to be aligned with the direct inhibition of the transport enzyme sodium/ potassium-ATPase. The decrease of sodium ions enhances the calcium ion concentration, which activates the myofibrillic enzyme and inactivates proteins like tropo-myocine and tropomine. Till present, a final proof for this hypothesis is lacking, the toxicity, however, is definitely aligned with these effects [97]. 

Na,K-ATPase sodium and potassium activated adenosine triphosphatase (Na pump)... 

The relationship of intracellular sodium to intracellular calcium is such that a very small increase in sodium in terms of percentage increase leads to a disproportionately large increase in calcium. Therefore, a direct effect on the sodium/potassium-ATPase to inhibit sodium pump activity is the primary mechanism of the positive inotropic effect of the cardiac glycosides, while secondary elevation of intracellular calcium provides the ionic punch to increase contractility. A diagram of the relationship between sodium/potassium-ATPase and calcium is shown in Figure 12.6. 

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