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Nature 320, 188 - 192 (13 March 1986); doi:10.1038/320188a0

Existence of distinct sodium channel messenger RNAs in rat brain

Masaharu Noda, Takayuki Ikeda, Toshiaki Kayano, Harukazu Suzuki, Hiroshi Takeshima, Mika Kurasaki, Hideo Takahashi & Shosaku Numa

Departments of Medical Chemistry and Molecular Genetics, Kyoto University Faculty of Medicine, Kyoto 606, Japan

The sodium channel is a voltage-gated ionic channel essential for the generation of action potentials1–3. It has been reported that the sodium channels purified from the electric organ of Electrophorus electricus (electric eel)4,5 and from chick cardiac muscle6 consist of a single polypeptide of relative molecular mass (M r) ~260,000 (260K), whereas those purified from rat brain7 and skeletal muscle8 contain, in addition to the large polypeptide, two or three smaller polypeptides of M r 37–45K. Recently, we have elucidated the primary structure of the Electrophorus sodium channel by cloning and sequencing the DNA complementary to its messenger RNA9. Despite the apparent homogeneity of the purified sodium channel preparations, several types of tetrodotoxin (or saxitoxin) binding sites or sodium currents have been observed in many excitable membranes10–19. The occurrence of distinguishable populations of sodium channels may be attributable to different states of the same channel protein or to distinct channel proteins. We have now isolated complementary DNA clones derived from two distinct rat brain mRNAs encoding sodium channel large polypeptides and present here the complete amino-acid sequences of the two polypeptides (designated sodium channels I and II), as deduced from the cDNA sequences. A partial DNA sequence complementary to a third homologous mRNA from rat brain has also been cloned.

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