Sodium-potassium ionic pump

FIGURE 17.2 Concept of a sodium-potassium ionic pump within flie phospholipid structure of flie cell membrane. The mcriecular pump structures are not exactly known. 

The ionic composition of the cell is maintained by operation of the sodium-potassium pump, which pumps ions from more dilute to more concentrated solutions the Na ions from the cytoplasm to the solution outside, and the K+ in the opposite... 

Membrane-bound enzymes, particularly the ATPases involved in the ionic pumps for calcium, sodium and potassium, have been found to function abnormally in the brains of epileptic patients and animals. A reduction in Na+K+-ATPase activity has been reported in human focal epileptogenic tissue, but it is uncertain whether such changes are due to the disease itself or a reflection of drug treatment. Similar changes have, however, been reported in experimental animals following the localized application of alumina cream and in DBA/2 mice that exhibit sound-induced seizures a reduction in calcium-dependent ATPase has also been found in the brain of DBA/2 mice. Such findings are consistent with the hypothesis that a defect in ion channels may occur in epilepsy. 

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. 

All cells, including muscle and nerve cells, have inside them an intracellular fluid (ICF) which contains high levels of potassium, K+, phosphate ions, PC>43+, and protein and small amounts of Na+ ions and chlorine ions. Outside the cells in the extracellular fluid (ECF) consists mostly of sodium ions, Na+, chloride, Cl, and bicarbonate ions, HC03, but no protein, plus low concentrations of potassium ions. The inner layer of the cell membrane is negatively charged relative to the outside. When activity occurs then an ionic pumping action takes place to try to maintain the balance within the cells between the intra and extra flow of sodium and potassium... 

Ionic pumps within membranes operate, over time, to produce markedly different concentrations of ions in the intracellular and extracellular volumes around cells. In cardiac cells, the sodium-potassium pump produces concentrations (millimoles per liter) for Purkinje cells as shown in Table 19.1. 

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

Potassium is accumulated within cells by the action of the Na. K -ATPase (sodium pump) in which it participates in exchange for sodium that is extruded from the cell during potassium uptake [10]. Potassium has a major function as a carrier of charge within cells [1]. It is extremely mobile and therefore if it is allowed to pass through membranes it may be used to regulate potentials across cells, especially excitable cells such as muscle and nerve [16]. The regulation of such metal ion flows, especially of potassium and sodium, is crucial to life and is most clearly exemplified by the ionic movements that occur in nerve cells during excitation and transmission of the action potential [17]. 

There are other aspects of the story, for example the fact that cyclic AMP also causes an extremely rapid, although smaller increase in rate of Rb uptake. However, space does not allow me to go into these matters. Let me summarize, then, by saying that serum has a remarkable effect upon quiescent 3T3 cells. In just a few minutes it causes the rate of entry of potassium (actually measured by using Rb) to increase by up to 3.5-4-fold. The effect is on Fmaz and is not due to synthesis of new transporter molecules. The stimulation is rapidly reversible on removal of serum, as if a switch were turned on and off—as if the transporter molecules were being rapidly uncovered and covered again. The effect is sensitive to ouabain, a specific inhibitor of the sodium-K pump. There is also an inhibition of initiation of DNA synthesis by ouabain, which is influenced by the level of K in the medium. It is presumed that a critical ionic environment is necessary for the events concerned in initiation of DNA synthesis, and the Na-K pump is involved in maintenance of this environment. 

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