Tubular apical

ENaC mediates Na+ entry from the tubule lumen at the apical membrane and the Na+/K+ ATPase extrudes Na+ at the basolateral side. K+ channels are present on the basolateral and apical membrane. K+ channels at the apical membrane mediate K+ secretion into the tubular lumen. 

Renal diseases Mutations in KCNJ1 disiupt the function of Kirl.l in apical renal outer medulla of the kidney. The loss of tubular K+ channel function and impaired K+ flux could prevent apical membrane potassium recycling and lead to antenatal Bartter s syndrome. 

The proximal tubular cell plays a major role in the elimination of both inorganic and organic substrates. The ceUs have two distinct membrane domains. The basolateral membrane is in contact with the blood, and the apical brush-border membrane lines the tubular lumen. 

Figure 5.10. Accumulation of a radiolabelled LMWP in the lysosomes of the proximal tubular cell. Electron microscope autoradiography of renal proximal tubular cells from a rat injected i.v. with [1251]-tyramine-cellobiose-labelled cytochrome-c, 4 h prior to fixation throngh the abdominal aorta. An intense lysosomal accumulation of the protein is observed in three dark electron-dense lysosomes. A few grains are seen over the apical endocytic apparatus. Part of the luminal brush border is found in the upper right hand corner. Magnification, x 25 000. Unpublished data from E. I. Christensen, Arhus, Denmark, and M. Haas, Groningen, Netherlands.

Because K+ does not recycle across the apical membrane of the DCT as it does in the TAL, there is no lumen-positive potential in this segment, and Ca2+ and Mg2+ are not driven out of the tubular lumen by electrical forces. Instead, Ca2+ is actively reabsorbed by the DCT epithelial cell via an apical Ca2+ channel and basolateral Na+/Ca2+ exchanger (Figure 15-4). This process is regulated by parathyroid hormone. 

As indicated earlier in this chapter, these transporter proteins are found in a variety of cell types but especially in those organs exposed to chemicals from the environment (e.g., gastrointestinal tract), excretory organs (e.g., kidney), and sensitive organs (e.g., brain). The proteins are usually found on the luminal side of epithelial cells in organs of exposure, such as the small intestine, which allows the cells to pump out the potentially hazardous chemical. In sensitive organs such as the brain, the transporters are on that side of cells that will allow chemicals to be pumped back into the blood or interstitial fluid. In organs of excretion, such as the kidney, the transporters are located on the apical side of cells such as the proximal convoluted tubular cells. 

These transporters can be responsible for the toxicity of some xenobiotics. For example, the drug cephaloridine is toxic to the kidney as a result of accumulation in the proximal tubular cells, which form the cortex of the kidney. The drug is a substrate for OAT-1 on the basolateral surface and hence is transported into the proximal tubular cells. However, the transport out of these cells from the apical surface into the lumen of the tubule is restricted, probably because of the cationic group on the molecule (Fig. 7.34). The toxicity of cephaloridine is modulated by chemicals that inhibit the OAT-1 and cation transporters. The similar drug cephalothin is not concentrated in the cells and is not nephrotoxic (Table 3.5). See chapter 7 for more details. 

Mechanism of action Acetazolamide inhibits carbonic anhydrase, located intracellularly and on the apical membrane of the proximal tubular epithelium (Figure 23.4). [Note Carbonic anhydrase catalyzes the reaction of C02 and H20 leading to H+ and HC03 (bicarbonate)]. The decreased ability to exchange Na+ for H+ in the presence of acetazolamide results in a mild diuresis. Additionally, HC03 is retained in the lumen with marked elevation in urinary pH. The loss of HCO3- causes a hyperchloremic... 

Renal proximal tubular epithelium (e.g., convoluted tubules) reclaim protein, including immunoglobulin, from the urinary filtrate via sorting/recy-cling mechanisms in intracellular vesicles. The apical (lumen-facing) surface of these cells features a specialized brush border which expresses FcRn closely associated with (S2-microglobulin [110,116], Studies with cultured human renal proximal tubular epithelial cells have demonstrated bidirectional IgG transport and salvage by fully functional FcRn [110] as discussed further in the next section. 

OCTN2 was identified as an Na+/camitine cotransporter and is also located in the apical membrane of proximal tubular cells. Substrates of OCTN2 are TEA, verapamil, pyrilamine, choline and quinidine (Koepsell et al. 2003). 

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