Na+/K+-antiporter

Transport of many compounds including drugs across cell membranes is mediated by membrane proteins called carrier proteins or channel proteins. Some of these proteins transport only one substrate molecule at a time across the membrane (uniport systems), while others act as cotransport systems (Figure 9.4). Depending on the direction of the second substrate, the proteins are also called symporters or antiporters, for example, Na /glucose cotransporter, H " /peptide cotransporter, or Na /K antiporter (—Na /K -ATPase). 

The main properties of the Na /K -antiporter-ATPase have been summarised as follows ... 

ATPase systems that are distinct from the Na /K" "-antiporter-ATPase of plasma membranes in being insensitive to ouabain , activated by but... 

The Na ion concentration within the cell is maintained low, due to activity of an enzyme known as the Na+/K+ ATPase. This enzyme/carrier is present in the plasma membrane. It is an antiport system that transports three Na+ ions out of the cell and two K+ ions into the cell, for each molecule of ATP that is hydrolysed (Figure 5.10). It is responsible for maintaining a low Na+ ion concentration but a high K+ ion concentration within the ceU. Its constant activity in many it not all cells requires constant ATP hydrolysis, which accounts for more than 10% of the resting energy expenditure of an adult. 

Sano, K., Cott, G., Voelker, D., and Mason, R. (1988). The Na+/H+ antiporter in rat alveolar type II cells and its role in stimulated sufactant secretion. Biochem. Biophys. Acta, 939, 449 158. 

There are, however, various types of active transport systems, involving protein carriers and known as uniports, symports, and antiports as indicated in Figure 3.7. Thus, symports and antiports involve the transport of two different molecules in either the same or a different direction. Uniports are carrier proteins, which actively or passively (see section "Facilitated Diffusion") transport one molecule through the membrane. Active transport requires a source of energy, usually ATP, which is hydrolyzed by the carrier protein, or the cotransport of ions such as Na+ or H+ down their electrochemical gradients. The transport proteins usually seem to traverse the lipid bilayer and appear to function like membrane-bound enzymes. Thus, the protein carrier has a specific binding site for the solute or solutes to be transferred. For example, with the Na+/K+ ATPase antiport, the solute (Na+) binds to the carrier on one side of... 

Neurons oxidize glucose by glycolysis and the citric acid cycle, and the flow of electrons from these oxidations through the respiratory chain provides almost all the ATP used by these cells. Energy is required to create and maintain an electrical potential across the neuronal plasma membrane. The membrane contains an electrogenic ATP-driven antiporter, the Na+K+ ATPase, which simultaneously pumps 2 K+ ions into and 3 Na+ ions out of the neuron (see Fig. 11-37). The resulting... 

Active transport of a solute against a concentration gradient also can be driven by a flow of an ion down its concentration gradient. Table 17.6 lists some of the active-transport systems that operate in this way. In some cases, the ion moves across the membrane in the opposite direction to the primary substrate (antiport) in others, the two species move in the same direction (symport). Many eukaryotic cells take up neutral amino acids by coupling this uptake to the inward movement of Na+ (see fig. 17.26c). As we discussed previously, Na+ influx is downhill thermodynamically because the Na+-K+ pump keeps the intracellular concentration of Na+ lower than the extracellular concentration and sets up a favorable electric potential difference across the membrane. Another example is the /3-galactosidc transport system of E. coli, which couples uptake of lactose to the inward flow of protons (see fig. 17.26Proton influx is downhill because electron-transfer reactions (or,... 

Active transport of a molecule across a membrane against its concentration gradient requires an input of metabolic energy. In the case of ATP-driven active transport, the energy required for the transport of the molecule (Na+, K+, Ca2+ or H+) across the membrane is derived from the coupled hydrolysis of ATP (e.g Na+/K+-ATPase). In ion-driven active transport, the movement of the molecule to be transported across the membrane is coupled to the movement of an ion (either Na+ or H+) down its concentration gradient. If both the molecule to be transported and the ion move in the same direction across the membrane, the process is called symport (e.g. Na+/glucose transporter) if the molecule and the ion move in opposite directions it is called antiport (e.g. erythrocyte band 3 anion transporter). 

Maly, K Oberhuber, H., Doppler, W Hoflacher, J., Jaggi, R., Groner, B., Grunicke, H. (1988). Effect of H-ras on phosphatidyl inositide metabolism, Na+/H+ antiporter and intracellular calcium. Adv. Enzyme Regul. 27, 121-143. 

Parallel activation of Na+/H+ antiport and CI7HCO3 antiport Erythrocytes from dog, rabbit, and Amphiuma lymphocytes osteoclasts endothelial cells parotis pancreas, liver, gallbladder, proximale tubule, medullary thick ascending limb, and collecting duct MDCK cells Activation of Na+-K+-2CI cotransport... 

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-... 

Aluminum in micromolar concentrations was found to inhibit calcium pumping in endoplasmic reticulum. The Ca2+ ATPase activity of rat brain and cerebellum was remarkably reduced and mitochondria showed increased Ca2+ release in the presence of exactly estimated 50 pmol L-1 Al3+ [67]. Aluminum was found to be an important disrupter of intracellular calcium homeostasis, interfering also with the mitochondrial Ca2+ pump, as well as activating an Na+-K+ ATPase - the antiport mechanism of ion exchange in the plasma membrane, which regulates the Ca2+-Na+ antiporter exchange [67]. 

Sodium Na+-H+ antiport and Na -glucose symport Re-absorbed, 65% Re-absorbed, 25%, ascending loop, Na+-K+ symport Re-absorbed, 5%, Na+-Cr symport Re-absorbed, 5%... 

Figure 6.8. Digitalis (foxglove) glycosides, a Mode of action. The drags inhibit the Na /K -ATP ase. The increased intracellular sodium concentration will reduce the activity of the Na /Ca antiport system and therefore lead to an increase of intracellular Ca and augment myofilament contraction, b Structures.

Cerebral tissue acidosis following ischemia or flaumatic brain injury contributes to cytotoxic brain edema formation. In vitro lactacidosis induces swelling of glial cells by intracellular Na" - and Cl accumulation by the Na" /H+-antiporter, Cr/HCOs antiporters, and the Na -K -2C1 cotransport (Staub et al., 1990 Ringel et al., 2006a). 

The sodium—calcium exchanger in the plasma membrane of an animal cell is an antiporter that uses the electrochemical gradient of Na+ to pump Ca2+ out of the cell. Three Na+ ions enter the cell for each ion that is extruded. The cost of transport by this exchanger is paid by the Na+-K+- ATPase pump, which generates the requisite sodium gradient. 

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