Sodium pump action

Figure 12.2 Mechanism of action of carbonic anhydrase inhibitors on the proximai convoiuted tubuie. Carbonic anhydrase is an enzyme that cataiyses the interconversion of C02and H20 to H2C03and is found in the iuminai epitheiium of the proximai, and to a iesser extent, the distai convoiuted tubuie. It is essentiai for the conservation of body base in the form of HCO-3. An antiporter (1) mechanism (the movement of substances across a barrier in opposite directions) exchanges fiitrate Na+for ceiiuiar H+. The H+combines with fiitrate HCO-3to form carbonic acid which is converted to C02and H20 in the presence of carbonic anhydrase (CA). The C02is reabsorbed by the ceii thereby conserving HCO-3. Acetazoiamide inhibits the activity of carbonic anhydrase and limits the conversion of HCO-3to absorbable C02. The concentration of HCO-3in the filtrate increases as does the urinary loss. P, the sodium pump ECF, extracellular fluid.

Figure 12.4 Mechanism of action of Na+/K+symport inhibitors (thiazides) on the distal convoluted tubule. As in the other parts of the nephron, Na+movement is powered by the energy-requiring sodium pump (P) in the basolateral membrane which exchanges intracellular Na+for K-i-in the extracellular fluid (ECF). The transport of Na-rand Cl- into the cell from the filtrate against the prevailing electrochemical gradient is facilitated by the symporter (S). The Na-Hons are then transported by the pump mechanism described above and the Cl- ions diffuse passively Into the ECF through ion channels in the basolateral membrane. Thiazide diuretics inhibit the symporter by disabling the Cl- binding site with the loss of Na-rand Cl- in the urine.

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility. Na+,K+ ATPase, the sodium pump, is the site of action of cardiac glycosides. NCX is the sodium, calcium exchanger. Cav-L is the voltage-gated, L-type calcium channel. SERCA (sarcoplasmic...

Digitoxin and its derivatives bind to the sodium-potassium pump and prevent it from exchanging sodium and potassium ions. When given in small quantities the result, especially in cardiac tissue, is that calcium ion content will be upset and calcium will be liberated from its stores. The newly available calcium can then interact with cardiac muscle protein to cause contraction. This is a therapeutic effect for those suffering from insufficient heart-pumping action (congestive heart failure or dropsy). The heart is made to contract efficiently and forcefully (inotropic effect). However, you can see that there may be a fine line between a necessary contraction and one which... 

In addition to the Na+,K+- ATPases there is a very active Ca2+-ATPase which transports two Ca2+ from the inside of cells to the outside while returning two H+ from outside per ATP.510 543a This is the primary transporter by which cells maintain a low internal [Ca2+]. During its action it becomes phosphorylated on Asp 351. However, in neurons, in which the membrane potential is maintained at a high negative value by the sodium pump, an Na+/ Ca2+ ion exchange plays an even more important role.540... 

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... 

The postulated mechanism of action of palytoxin is to bind to the mammalian Na-K-ATPase (or sodium pump) and convert this enzyme into an open channel. However, the ubiquity of pumps and channels in the living tissues and the high diversity of preparations nsed to study the mechanism of action of palytoxin make it difficult to rule out the possibility that another site may be involved. In this sense, recent evidences indicate that the Na-K-ATPase may not be the only target of the toxin. It must be pointed out that the vast majority of work performed to test the mechanism of action of palytoxin had relied on the initial experiments indicating palytoxin binding to Na-K-ATPase (Bottinger and Habermaim 1984 Bottinger et al. 1986). 

This section will start with a short review of the functioning of the sodium pump and then examine the main evidence supporting an action of the toxin in the sodium pump or in other cellular targets. 

Some 65% of the filtered sodium is actively transported from the lumen of the proximal tubule by the sodium pump (Na", K -ATPase). Chloride is absorbed passively, accompan)dng the sodium bicarbonate is also absorbed, through the action of carbonic anhydrase. These solute shifts give rise to the iso-osmotic reabsorption of water, with the result that > 70% of the glomerular filtrate is returned to the blood from this section of the nephron. The epithelium of the proximal tubule is described as leaky because of its free permeability to water and a number of solutes. Osmotic diuretics such as mannitol are solutes which are not reabsorbed in the proximal tubule (site 1. Fig. 26.1) and therefore retain water in the tubular fluid. Their effect is to increase water rather than sodium loss, and this is reflected in their special use acutely to reduce intracranial or intraocular pressure and not states associated with sodium overload. 

Fischer, P. W., and Giroux, A. (1987). Effects of dietary magnesium on sodium-potassium pump action in the heart of rats. /. Nutr. 117, 2091-2095. 

Carbohydrates, or starches, which are complex polysaccharides, are hydrolyzed to oligosaccharides and disaccharides by the action of pancreatic amylase. Disaccharides, including lactase, sucrase, and maltase, are enzymatically split by enzymes contained in the microvilli of enterocytes. Glucose and other monosaccharides are absorbed by an active transport mechanism and this action is coupled to energy derived from a sodium pump mechanism. 

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