Distal convoluted tubule, transport mechanisms

In distal convoluted tubules, calcium is transported by an active transport mechanism through rather than between cells. Moreover, in distal convoluted tubules there is a reciprocal relation between the direction and magnitude of calcium on Na+ transport. As Na+ absorption increases, calcium decreases, and conversely, reductions of Na+ absorption are accompanied by elevated calcium reabsorption. This interaction has important implications for diuretics acting in the distal convoluted tubule. 

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.

Only about 10% of the filtered NaCI is reabsorbed in the distal convoluted tubule (DCT). Like the TAL of Henle s loop, this segment is relatively impermeable to water and NaCI reabsorption further dilutes the tubular fluid. The mechanism of NaCI transport in the DCT is an electrically neutral thiazide-sensitive Na+ and cotransporter (NCC, Figure 15-4). 

Because K+ does not recycle across the apical membrane of the distal convoluted tubule as it does in the loop of Henle, there is no lumen-positive potential in this segment, and Ca2+ and Mg2+ are not driven out of the tubular lumen by electrical forces. However, Ca2+ is actively reabsorbed by the distal convoluted tubule epithelial cell via an apical Ca2+ channel and basolateral Na+/Ca2+ exchanger (Figure 15-5). This process is regulated by parathyroid hormone. As will be seen below, the differences in the mechanism of Ca2+ transport in the distal convoluted tubule and in the loop of Henle have important implications for the effects of various diuretics on Ca2+ transport. 

Figure 10.1 Sites and mechanisms of action of diuretics. The location of each cell type along the nephron is indicated by the shading patterns. Spironoiactone (not shown) is a competitive aldosterone antagonist and acts primarily in the collecting duct. PT, proximal tubule LH, loop of Henie TAL, thick ascending limb DT, distal tubule DCT, distal convoluted tubule CD, collecting duct PC, principal cell CA, carbonic anhydrase CAI, carbonic anhydrase inhibitors , primary active transport. (Adapted with permission from Ellison D H 1991 The physiologic basis of diuretic synergism its role in treating diuretic resistance. Annals of Internal Medicine 114 886-894.)...

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.)...

To understand the mechanism of urine concentration, one must retrace the fate of the fluid in the various segments of the kidney. In the glomerulus, the membranes of the Bowman s capsule cells allow passage of all plasma components except protein. The ultrafiltrate is markedly reduced in volume as it passes through the proximal tubule. In fact, only 20% of the original volume reaches the distal portion of the proximal convoluted tube. The volume of the ultrafiltrate is reduced due to passive water reabsorption. Passive means that no known molecular mechanism exists for the transport of water from the lumen of the proximal tubule to the interstitial tissue. However, the movement of water follows that of sodium. In the proximal tubule, sodium is excreted actively into the interstitial tissue, and as a result, the osmotic pressure of the interstitial tissues increases. This draws water from the lumen of the tubule into the interstitial environment of the medulla because the tubule is highly permeable to water. 

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