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Primary structure of the adult human skeletal muscle voltage‐dependent sodium channel
Author(s) -
George Alfred L.,
Komisarof Jeffrey,
Kallen Roland G.,
Barchi Robert L.
Publication year - 1992
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410310203
Subject(s) - sodium channel , skeletal muscle , tetrodotoxin , medicine , endocrinology , biology , gene product , muscle contraction , gene , microbiology and biotechnology , sodium , biochemistry , chemistry , gene expression , organic chemistry
The gene encoding the principal voltage‐dependent sodium channel expressed in adult human skeletal muscle (SCN4A) has recently been linked to the pathogenesis of human hyperkalemic periodic paralysis and paramyotonia congenita. We report the cloning and nucleotide sequence determination of the normal product of this gene. The 7,823 nucelotide complementary DNa, designated hSkM1, encodes a 1,836 amino acid protein that exhibits 92% identity with the tetrodotoxin‐senstive rat skeletal muscle sodium channel alpha subunit, but lower homology with either the human heart sodium channel or with other sodium channels from immature rat muscle or rat brain. Specific hSkM1 RNA trasnscripts are expressed in adult human skeletal muscle but not in heart, brain, or uterus. The SCN4A gene product, hSkM1, is the human homologue of rSkM1, the tetrodotoxin‐sensitive sodium channel characteristic of adult rat skeletal muscle. This structural information should provide the necessary backdrop for identifying and evaluating mutations affecting the function of this channel in the periodic paralyses.