Transporters sodium-calcium exchanger

This antiporter (NCX) uses the sodium gradient to move calcium against its concentration gradient from the cytoplasm to the extracellular space. Extracellular concentrations of these ions are much less labile than intracellular concentrations under physiologic conditions. The sodium-calcium exchanger s ability to carry out this transport is thus strongly dependent on the intracellular concentrations of both ions, especially sodium. 

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility (numbered structures). Site 1 is Na+/K+ ATPase, the sodium pump. Site 2 is the sodium/calcium exchanger. Site 3 is the voltage-gated calcium channel. Site 4 is a calcium transporter that pumps calcium into the sarcoplasmic reticulum (SR). Site 5 is a calcium channel in the membrane of the SR that is triggered to release stored calcium by activator calcium. Site 6 is the actin-troponin-tropomyosin complex at which activator calcium brings about the contractile interaction of actin and myosin.

The SR membrane contains a very efficient calcium uptake transporter, which maintains free cytoplasmic calcium at very low levels during diastole by pumping calcium into the SR. The amount of calcium sequestered in the SR is thus determined, in part, by the amount accessible to this transporter. This in turn is dependent on the balance of calcium influx (primarily through the voltage-gated membrane calcium channels) and calcium efflux, the amount removed from the cell (primarily via the sodium-calcium exchanger, a transporter in the cell membrane). 

Matsuoka, S. Hilgemann, D.W. (1992). Steady-state and dynamic properties of cardiac sodium-calcium exchange. Ion and voltage dependencies of the transport cycle. J. Gen. Physiol. 100, 963-1001. 

Philipson, K.D. Nicoll, D.A. (1992). Sodium-calcium exchange. Curr. Op. Cell Biol. 4,678-683. Reeves, J.P. (1985). The sarcolemmal sodium-calcium exchange system. Curr. Top. Membr. Transport 25,77-127. 

Figure 7.5 Cartoon (left) and mechanism (right) for sodium-calcium exchanger. This electrogenic transporter exchanges 3 Na+ ions for 1 Ca2+ ion.

Exchange- and co-transporters. These link the gradients of different ion species to one another, so that gradients can be established for ions for which specific pumps do not exist (or have insufficient capacity). Important examples are the sodium/calcium exchanger and the potas-sium/chloride co-transporter in the cytoplasmic membrane (Figure 4.1). 

Energy for transport by pumps may be derived from ATP hydrolysis or from the ionic gradients of another ion. This is the case of the sodium/calcium exchanger, which uses the electrical energy stored in the sodium gradient across the plasma membrane to transport calcium out of the cell while harnessing the energy from concerted sodium influx (Komuro et al, 1992). 

A different mechanism of active transport, one that utilizes the gradient of one ion to drive the active transport of another, will be illustrated by the sodium—calcium exchanger. This pump plays an important role in extruding Ca2+ from cells. 

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. 

Sodium-calcium exchanger A transport molecule in the membrane of many cells (eg, cardiac cells) that pumps one calcium atom against its concentration gradient (outward) in exchange for 3 sodium ions (moving inward, down their concentration gradient)... 

Figure 15-5. Mechanism of sodium and chloride reabsorption in the distal convoluted tubule. A separate reabsorptive mechanism, modulated by parathyroid hormone, is present for movement of calcium into the cell from the urine. This calcium must be transported via the sodium-calcium exchanger back into the blood. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

B. Effects In full doses, thiazides produce moderate but sustained sodium and chloride diuresis. Hypokalemic metabolic alkalosis may occur (Table 15-2). Reduction in the transport of sodium into the tubular cell reduces intracellular sodium and promotes sodium-calcium exchange. As a result, reabsorption of calcium from the urine is increased and urine calcium content is decreased— the opposite of the effect of loop diuretics. Because they act in a diluting segment of the nephron, thiazides may interfere with excretion of water and cause dHutional hyponatremia. 

Answer (a) is incorrect. The sodium-calcium exchanger transports these cations in the opposite direction therefore, it is an antiporter, not a symporter. 

Powis, D. A. Clark, C. L. et al. (1994). "Lanthanum ean be transported by the sodium-calcium exchange pathway and direetly triggers cateeholamine release from bovine chromaffin cells." Cell Calcium, 16(5), 377-90. 

Intracellular fluids (also called the cytosol) are quite different compositionally from plasma and interstitial fluids (Table 4, Figures 4 and 5). The internal pH of many cells is maintained near 6.9-7.0. via various membrane transport mechanisms such as Na" /H and CP/HCO exchangers, and various phosphate and protein buffers. In contrast to the plasma, the intracellular fluids have substantially lower concentrations of sodium, calcium, chloride, and bicarbonate and higher to substantially higher concentrations of potassium, magnesium,... 

Fig. 2.5. Interaction of Ca transport with the proton circuit, a, Ca uptake alone discharges the membrane potential b, Ca uptake in exchange for protons extruded by the respiratory chain generates a pH gradient c, Ca uptake together with a weak acid such as acetate does not build up a pH gradient d, Ca cycling in heart mitochondria driven by the proton circuit. R, respiratory chain C, calcium uniport NH, sodium/proton antiport NC, sodium/calcium antiport.

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. 

Interference withcaldiantraniport Some eviderKe indicates that ionophores may alter calcium transport by changing the sodium component of the s iunv-calcium exchange diffusion carrier in cell membranes, le ing tofiie accumula> tion of calcium in the cells and mitochondria and pOKiUy causii cell death. 

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. 

The outer membrane, the plasmalemma, efficiently protects the cell from the environment while, at the same time, carrying out functions important for cell metabolism the uptake of substrates and the elimination of toxic compounds. Substrate exchange with the environment is controlled by transport proteins embedded in the membrane (energy-requiring pumps such as Na+,K+-ATPase, or other transport units such as the Na+/glucose cotransporter and sodium and calcium ion channels) [1],... 

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