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Molecular cloning, functional expression and chromosomal localization of an amiloride‐sensitive Na + channel from human small intestine
Author(s) -
Schaefer Lionel,
Sakai Hideki,
Mattei Marie-Geneviève,
Lazdunski Michel,
Lingueglia Eric
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01403-4
Subject(s) - amiloride , acid sensing ion channel , xenopus , epithelial sodium channel , ion channel , microbiology and biotechnology , sodium channel , biology , extracellular , mechanosensitive channels , chemistry , biochemistry , gene , receptor , sodium , organic chemistry
Amiloride‐sensitive Na + channels belonging to the recently discovered NaC/DEG family of genes have been found in several human tissues including epithelia and central and peripheral neurons. We describe here the molecular cloning of a cDNA encoding a novel human amiloride‐sensitive Na + channel subunit that is principally expressed in the small intestine and has been called hINaC ( uman ntestine + hannel). This protein is similar to the recently identified rodent channel BLINaC and is relatively close to the acid sensing ion channels (ASICs) (79 and 29% amino acid identity, respectively). ASICs are activated by extracellular protons and probably participate in sensory neurons to nociception linked to tissue acidosis. hINaC is not activated by lowering the external pH but gain‐of‐function mutations can be introduced and reveal when expressed in Xenopus oocytes, an important Na + channel activity which is blocked by amiloride (IC 50 =0.5 μM). These results suggest the existence of a still unknown physiological activator for hINaC (e.g. an extracellular ligand). The presence of this new amiloride‐sensitive Na + channel in human small intestine probably has interesting physiological as well as physiopathological implications that remain to be clarified. The large activation of this channel by point mutations may be associated with a degenerin‐like behavior as previously observed for channels expressed in nematode mechanosensitive neurons. The hINaC gene has been mapped on the 4q31.3–q32 region of the human genome.