Sodium-potassium ATPase activity

In vitro experiments have shown that vanadium as vanadate inhibits sodium-potassium ATPase activity and thus inhibits the sodium potassium pump (Nechay and Saunders 1978). This pump is necessary for proper transport of materials across cell membranes. The kidney (Higashino et al. 

The disturbance in the membrane potential difference is corrected by hemodialysis or protein restriction, suggesting a causative role for dialyzable products of protein metabolism. Phenolic acids (W2), methylguanidine, atriopeptins, and tissue hypothyroidism have been suggested as causes for the decreased sodium potassium ATPase activity (C23). 

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... 

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. 

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]. 

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. 

Many substances can be transported into the cell (and vice versa) against a concentration gradient. This is an active transport process, and it requires energy in the form of ATR It is to be distinguished from a passive transport process, which is simple diffusion across membranes. One of the better understood systems of this type is the sodium-potassium ATPase (or Na/K) pump, which maintains high potassium and low sodium levels in the cell. These are up to 160 meq/L for K+ and about 10 meq/L of Na+ inside the cell. Extracellular fluid contains about 145 meq/L of Na+ and 4 meq/L of K+. The simultaneous movement of one substance out of the cell and another into the cell is an antiport. A substantial percentage of the basal metabolic rate (see Chapter 21) is accounted for by the activity of the Na/K pump. ATPase (Na/K pump) is lo-... 

The plasma membrane of neurons, like all other cells, has an unequal distribution of ions and electrical charges between its two sides. Sodium-potassium ATPase pumps maintain this unequal concentration by actively transporting ions against their concentration gradients sodium in, potassium out. The membrane is positive outside and negative inside. This charge difference is referred to as the resting potential and is measured in millivolts (=—65 mV). 

Further sequelae to lipid peroxidation include inhibition of membrane-bound, phospholipid-dependent sodium-potassium ATPase and calcium ATPase with changes in the electrolyte milieu, especially calcium overloading of the cell with subsequent further cell damage and cell death as well as inhibition of adenylate cyclase. This results in loss of function in the mitochondria and microsomes. Damage to the DNA leads to enzyme defects or impaired enzyme synthesis, which triggers further metabolic changes. This also causes a cellular overload with calcium and subsequent activation of... 

Decreased activity of the enzyme sodium potassium ATPase increases cellular sodium and decreases potassium, resulting in a decreased potential difference across the cell membrane. Because cellular sodium gain exceeds potassium loss, the cell water content increases. The decreased enzyme activity and the derangement in cell sodium, potassium, and water content are corrected partially by hemodialysis and completely by renal transplantation (C22, P3). 

Figure 8.9. Physiology and molecular biology of intestinal bile acid transport. Bile acids are actively absorbed in enterocytes through a sodium-dependent cotransporter, ASBT. The sodium gradient is maintained by the sodium-potassium ATPase, located at the basolateral membrane. In the ( osol, bile acids are shuttled through the cell by the aid of various proteins, most importantly the ileal hille acid binding protein, iBABP. An anion exchanger transports bile acids across the basolateral membrane into the portal circulation.

Lithium readily enters excitable cells via sodium channels. It is not. however, removed well by the sodium/potassium ATPase exchange mechanism. It therefore accumulates within the cell. Thus, the intracellular concentration of potassium is decreased as the influx of potassium is reduced, both through inhibition of active transport (by Na+/K+ ATPase) and the decrease in the electrical gradient for potassium. Extracellular potassium therefore increases. The reversal in potassium levels results in a decrease in neuronal excitability, producing a therapeutic calming effect. 

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