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J Physiol Volume 519, Number 2, 323-333, September 1, 1999
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The Journal of Physiology (1999), 519.2, pp. 323-333
© Copyright 1999 The Physiological Society

Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals

Hideki Sakai *, Eric Lingueglia *, Guy Champigny *, Marie-Geneviève Mattei ¹ and Michel Lazdunski *

* Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne and ¹ INSERM U 491, 27 Boulevard Jean Moulin, 13385 Marseille cedex, France


A degenerate polymerase chain reaction (PCR) homology screening procedure was applied to rat brain cDNA in order to identify novel genes belonging to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family of ion channels. A single gene was identified that encodes a protein related to but clearly different from the already cloned members of the family (18-30 % amino acid sequence identity). Phylogenetic analysis linked this protein to the group of ligand-gated channels that includes the mammalian acid-sensing ion channels and the Phe-Met-Arg-Phe-amide (FMRFamide)-activated Na+ channel.


Expression of gain-of-function mutants after cRNA injection into Xenopus laevis oocytes or transient transfection of COS cells induced large constitutive currents. The activated channel was amiloride sensitive (IC50, 1·31 µM) and displayed a low conductance (9-10 pS) and a high selectivity for Na+ over K+ (ratio of the respective permeabilities, PNa+/PK+ 10), all of which are characteristic of NaC/DEG channel behaviour.


Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed a predominant expression of its mRNA in the small intestine, the liver (including hepatocytes) and the brain. This channel has been called the brain-liver-intestine amiloride-sensitive Na+ channel (BLINaC).


Corresponding gain-of-function mutations in Caenorhabditis elegans degenerins are responsible for inherited neurodegeneration in the nematode. Besides the BLINaC physiological function that remains to be established, mutations in this novel mammalian degenerin-like channel might be of pathophysiological importance in inherited neurodegeneration and liver or intestinal pathologies.


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