Cell Sodium potassium ATPase

Apical membrane Na+/H+ exchange (via NHE3) and bicarbonate reabsorption in the proximal convoluted tubule cell. Na+/K+ ATPase is present in the basolateral membrane to maintain intracellular sodium and potassium levels within the normal range. Because of rapid equilibration, concentrations of the solutes are approximately equal in the interstitial fluid and the blood. Carbonic anhydrase (CA) is found in other locations in addition to the brush border of the luminal membrane. 

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). 

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). 

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. 

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. 

Additional cellular events linked to the activity of blood pressure regulating substances involve membrane sodium transport mechanisms Na+/K.+ ATPase Na+fLi countertransport Na+ -H exchange Na+-Ca2+ exchange Na+-K+ 2C1 transport passive Na+ transport potassium channels cell volume and intracellular pH changes and calcium channels. 

Inhibition of the Na+/K+-ATPase leads to a loss of potassium and an increase of sodium within the cell. Secondary intracellular calcium is increased via the Na VCa -exchanger. This results in a positive inotropic effect in the myocardium, with an increase of peak force and a decrease in time to peak tension. Besides this, cardiac glycosides increase vagal activity by effects on the central vagal nuclei, the nodose ganglion and increase in sensitivity of the sinus node to acetylcholine. 

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]. 

The ventricular action potential is depicted in Fig. 6-2.2 Myocyte resting membrane potential is usually -70 to -90 mV, due to the action of the sodium-potassium adenosine triphosphatase (ATPase) pump, which maintains relatively high extracellular sodium concentrations and relatively low extracellular potassium concentrations. During each action potential cycle, the potential of the membrane increases to a threshold potential, usually -60 to -80 mV. When the membrane potential reaches this threshold, the fast sodium channels open, allowing sodium ions to rapidly enter the cell. This rapid influx of positive ions... 

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. 

An essential requirement for diffusion of Na+ ions is the creation of a concentration gradient for sodium between the filtrate and intracellular fluid of the epithelial cells. This is accomplished by the active transport ofNa+ ions through the basolateral membrane of the epithelial cells (see Figure 19.4). Sodium is moved across this basolateral membrane and into the interstitial fluid surrounding the tubule by the Na+, K+-ATPase pump. As a result, the concentration of Na+ ions within the epithelial cells is reduced, facilitating the diffusion of Na+ ions into the cells across the luminal membrane. Potassium ions transported into the epithelial cells as a result of this pump diffuse back into the interstitial fluid (proximal tubule and Loop of Henle) or into the tubular lumen for excretion in the urine (distal tubule and collecting duct). 

Pumps move ions and molecules up their electrochemical gradient. Pumps require energy, usually in the form of ATP hydrolysis. Sodium-potassium ATPase is an example of a pump. Cells maintain a higher concentration of potassium inside the cell than they do outside the cell. Sodium is maintained low inside, high outside. Sodium-potassium ATPase pumps three sodium ions from inside the cell to outside. This is the unfavorable direction—Na+ moves from low concentration to a higher one and against the membrane potential. At the same time, it also... 

Glitsch, H. G. Electrophysiology of the sodium-potassium -ATPase in cardiac cells. Physiol. Rev. 81 1791-1826,2001. 

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. 

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

There is reason to beheve that cardiac glycosides, like other inotropic substances, act on the contractibility of the heart by affecting the process of calcium ion transfer through the membrane of myocardiocytes. The effect of cellular membranes in electric conductivity is mediated by transport of sodium, calcium, and potassium ions, which is a result of indirect inhibitor action on the (Na+-K+) ATPase of cell membranes. 

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. 

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