Active transport, ions across cell membranes

If osmosis and simple diffusion were the only mechanisms for transporting water and ions across cell membranes, these concentration differences would not occur. One positive ion would be just as good as any other. However, the situation is more complex than this. Large protein molecules embedded in cell membranes actively pump sodium ions to the outside of the cell and potassium ions into the cell. This is termed active transport because cellular energy must be expended to transport those ions. Proper cell function in the regulation of muscles and the nervous system depends on the sodium ion/potassium ion ratio inside and outside of the cell. 

The Na, K-ATPase is the cation-activated membrane enzyme that pumps Na+ and K+ ions across cell membranes when ATP is split. The hydrolysis of ATP provides enough energy to transport the ions against their electrochemical gradients, but the mechanism is not understood. Because the protein components of the enzyme operate across the membrane, the physical chemistry of channel processes discussed here may provide some insight into possible mechanisms. 

The GSH reductase inhibitor l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) also promotes corneal swelling in the isolated cornea. The addition of GSH prevents the action of BCNU as the cornea needs a constant supply of NADPH for maintaining adequate concentrations of reduced glutathione for the detoxification of hydrogen peroxide. It has been shown that hydrogen peroxide and BCNU primarily affect the permeability of the endothelial cells rather than the active processes transporting sodium and chloride ions across the membrane (Riley, 1985). 

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 Na+-K+ pump also plays a vital role in this process. For each molecule of ATP expended, three Na+ ions are pumped out of the cell into the ECF and two K+ ions are pumped into the cell into the ICF. The result is the unequal transport of positively charged ions across the membrane such that the outside of the cell becomes more positive compared to its inside in other words, the inside of the cell is more negative compared to the outside. Therefore, the activity of the pump makes a small direct contribution to generation of the resting membrane potential. 

Most human cells are exposed to less than 2 mM Li+, and in most tissues the intracellular Li+ concentration is lower than the extracellular concentration. The level inside cells is generally below that expected for the passive diffusion of the Li+ ion across the cell membrane, indicating that Li+ is actively transported out of cells. For instance, the concentration of Li+ inside the erythrocytes from people taking lithium salts is low with a typical ratio of intra- to extracellular Li+ of 0.5 [53]. 

For a cell membrane in a living animal, a very slight pressure difference will activate transport processes in the membrane, which will effectively eliminate the pressure difference. Introducing this change, there is no longer a state of equilibrium across the membrane, and other transport processes will take place. Such transport often is supported by chemical pumps, which move sodium ions from the protein phase to the aqueous phase. The simple estimation above illustrates that relatively small changes in the concentration are necessary to eliminate the osmotic pressure. In order to force PB — PA = 0, c(Na) in phase B must be reduced by 11 mmol/L, or by less than 10% of the previously determined concentration of 128 mmol/L (Gaiby and Larsen, 1995). 

Membrane proteins carry out a wide range of critical functions in cells, and they include passive and active transporters, ion chamiels, many classes of receptors, cellular toxins, proteins involved in membrane trafficking, and the enzymes that facilitate electron transport and oxidative phosphorylation. For example, the voltage-gated ion channels that facilitate the passive diffusion of sodium and potassium across the axonal membrane are responsible for the formation of an action potential. Active transport proteins establish ion gradients and are necessary for the uptake of nutrients into cells. Soluble hormones bind to membrane receptors, which then regulate the internal biochemistry of the cell. 

Figure 20-9 a a. Movement of Na and K ions across a membrane because of differences in concentration. b. Attraction of positive ions into a cell by electrostatic attraction and their removal by active transport... 

In muscle and adipose tissue, insulin promotes transport of glucose and other monosaccharides across cell membranes it al.so facilitates tran.sport of amino icids, potassium ion.s. nucleosides, and ionic phosphate. Insulin also activates certain enzymes—kinases and glycogen. synthetase in muscle und adipose tissue. In adipose tissue, insulin decreases the release of fatty acids induced by epinephrine or glucagon. cAMP promotes fatty acid release from adipose ti.ssue therefore. it is pos.sible that insulin decreases fatty acid release by reducing tissue levels of cAMP. Insulin also facilitates the incorporation of intracellular amino acids into protein. 

Cells move ions (especially Na+ and K" ") against a concentration gradient by a sodium pump that actively transports sodium across the plasma membranes (Chapter 12). 

These reactions take place in the blood plasma bathing the cells in the mucosa. By a process known as active transport, ions move across the membrane into the stomach interior. (Active transport processes are aided by enzymes.) To maintain electrical balance, an equal number of Cl ions also move from the blood plasma into the stomach. Once in the stomach, most of these ions are prevented from diffusing back into the blood plasma by cell membranes. 

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