Epithelial sodium channel related to proteins involved in neurodegeneration

• Published in: Nature (London) Vol. 361; no. 6411; pp. 467 - 470
• Main Authors: Canessa, Cecilia M, Horisberger, Jean-Daniel, Rossier, Bernard C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 04-02-1993; Nature Publishing Group
• Subjects: Absorption; Amiloride - pharmacology; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Caenorhabditis elegans - genetics; cDNA; colon; Colon - chemistry; Deoxyribonucleic acid; Digestive system; DNA; DNA - genetics; DNA - isolation & purification; Epithelium - chemistry; expression; Fundamental and applied biological sciences. Psychology; Gene Expression; genes; Intestinal Mucosa - chemistry; Intestine. Mesentery; Molecular Sequence Data; Nerve Degeneration - physiology; neurodegeneration; nucleotide sequence; Oocytes - metabolism; predictions; Proteins; Rats; Rodents; Sequence Homology; Sodium - metabolism; sodium channels; Sodium Channels - chemistry; Sodium Channels - genetics; Sodium Channels - physiology; Transfection; Vertebrates: digestive system; Xenopus; Heterologous system; Rat; Digestive system; Gut; Rodentia; Sequence alignment; Electrophysiology; Primary structure; Ionic channel; Gene expression; Vertebrata; Regulation(control); Mammalia; Gene; Sodium; Epithelial cell; Multigene family; Colon; Molecular cloning; Cell volume
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/361467a0

The epithelial amiloride-sensitive sodium channel constitutes the rate limiting step for sodium reabsorbtion by the epithelial lining the distal part of the kidney tubule, the urinary bladder and the distal colon. Reabsorbtion of sodium through this channel, which is regulated by hormones such as aldosterone and vasopressin, is one of the essential mechanisms involved in the regulation of sodium balance, blood volume and blood pressure. Here we isolate a DNA from epithelial cells of rat distal colon and identify it by functional expression of an amiloride-sensitive sodium current in Xenopus oocyte. The deduced polypeptide (698 amino acids) has at least two putative transmembrane segments. Expression of this protein in Xenopus oocytes reconstitutes the functional properties of the highly selective amiloride-sensitive, epithelial sodium channel. The gene encoding this rat sodium channel subunit shares significant sequence similarity with mec-4 and deg-1, members of a family of Caenorhabditis elegans genes involved in sensory touch transduction and, when mutated, neuronal degeneration. We propose that the gene products of these three genes are members of a gene family coding for cation channels.