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| THE NA-K-CL COTRANSPORTERS |
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| Author(s): HAAS M |
| Source: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Volume: 267 Issue: 4 Pages: C869-C885 Published: OCT 1994 |
| Times Cited: 132 References: 143 |
| Abstract: The Na-K-Cl cotransporters are a class of membrane proteins that transport Na, K, and Cl ions into and out of cells in an electrically neutral manner, in most cases with a stoichiometry of 1Na:1K:2Cl. Na-K-Cl cotransporters are present in a wide variety of cells and tissues, including reabsorptive and secretory epithelia, nerve and muscle cells, endothelial cells, fibroblasts, and blood cells. Na-K-Cl cotransport plays a vital role in renal salt reabsorption and in salt secretion by intestinal, airway, salivary gland, and other secretory epithelia. Cotransport function also appears to be important in the maintenance and regulation of cell volume and of ion gradients by both epithelial and nonepithelial cells. Na-K-Cl cotransport activity is inhibited by ''loop'' diuretics, including the clinically efficacious agents bumetanide and furosemide. The regulation of Na-K-Cl cotransport is mediated, at least in some cases, through direct phosphorylation of the cotransport protein. Cotransporter regulation is highly tissue specific, perhaps in part related to the presence of different Na-K-Cl cotransporter isoforms. In epithelia, both absorptive (kidney-specific) and secretory isoforms have been identified by cDNA cloning and sequencing and Northern blot analysis; alternatively spliced variants of the kidney-specific isoform have also been identified. The absorptive and secretory isoforms exhibit similar to 60% identity at the amino acid sequence level; these sequences in turn show similar to 45% overall homology with those of thiazide-sensitive, bumetanide-insensitive, Na-Cl cotransport proteins of winter flounder urinary bladder and mammalian kidney. This review focuses on recent developments in the identification of Na-K-Cl cotransport proteins in epithelia and on the regulation of epithelial Na-K-Cl cotransporter function at cellular and molecular levels. |
| Document Type: Review |
| Language: English |
| Reprint Address: HAAS, M (reprint author), UNIV CHICAGO, DEPT PATHOL, MC 3083, 5841 S MARYLAND AVE, CHICAGO, IL 60637 USA |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Cell Biology; Physiology |
| IDS Number: PW517 |
| ISSN: 0363-6143 |
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