期刊
ANNUAL REVIEW OF PHYSIOLOGY
卷 62, 期 -, 页码 515-+出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.physiol.62.1.515
关键词
ion transport; K-Cl cotransport; bumetanide; furosemide; chloride
类别
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK047661] Funding Source: NIH RePORTER
- NIDDK NIH HHS [DK-47661] Funding Source: Medline
The Na-K-Cl cotransporters are a class of ion transport proteins that transport Na, K, acid Cl ions into and out of cells in an electrically neutral manner, in most eases with a stoichiometry of 1Na:1K:2Cl. To date, two Na-K-Cl cotransporter isoforms have been identified: NKCC1, which is present in a wide variety of secretory epithelia and non-epithelial cells; and NKCC2, which is present exclusively in the kidney, in the epithelial cells of the thick ascending limb of Henle's loop and of the macula densa. Both NKCC isoforms represent part of a diverse family of cation-chloride cotransport proteins that share a common predicted membrane topology; this family also includes Na-Cl cotransporters and multiple K-Cl cotransporter isoforms. In secretory epithelia, the regulation of NKCC1, which is typically present on the basolateral membrane, is tightly coordinated with that of other transporters, including apical Cl channels, to maintain cell volume and integrity during active salt and fluid secretion. Changes in intracellular [Cl] ([Cl](i)) appear to be involved in this regulation of NKCCI, which is directly phosphorylated by an unknown protein kinase in response to various secretagogues as well as reductions in [Cl](i) and cell volume. This review focuses on structure-function relationships within NKCC1 and on recent developments pertaining to NKCC1 regulation at cellular and molecular levels.
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