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Letters to Nature
Nature 322, 826 - 828 (28 August 1986); doi:10.1038/322826a0

Expression of functional sodium channels from cloned cDNA

Masaharu Noda, Takayuki Ikeda, Harukazu Suzuki, Hiroshi Takeshima, Tomoyuki Takahashi*, Motoy Kuno* & Shosaku Numa

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

The voltage-gated sodium channel is a transmembrane protein essential for the generation of action potentials in excitable cells1. It has been reported that sodium channels purified from the electric organ of the electric eel, Electrophorus electricus2,3, and from chick cardiac muscle4 consist of a single polypeptide of relative molecular mass (M r)~ 260,000, whereas those purified from rat brain5 and from rat6,7 and rabbit skeletal muscle7 contain, in addition to the large polypeptide, one or two smaller polypeptides of M r33,000–43,000. The primary structures of the Electrophorus sodium channel8 and two distinct sodium channel large polypeptides9 (designated as sodium channels I and II) from rat brain have been elucidated by cloning and sequencing the complementary DNAs. The purified sodium channel preparations from Electrophorus electroplax10 and from mammalian muscle11,12 and brain13–15, when reconstituted into lipid vesicles or planar lipid bilayers, exhibit some functional activities. The successful reconstitution with the Electrophoruspreparation would imply that the large polypeptide alone is sufficient to form functional sodium channels. However, studies with the rat brain preparation suggest that the smaller polypeptide of M r36,000 is also required for the integrity of the saxitoxin (STX) or tetrodotoxin (TTX) binding site of the sodium channel16. Here we report that the messenger RNAs generated by transcription of the cloned cDNAs encoding the rat brain sodium channel large polypeptides, when injected into Xenopus oocytes, can direct the formation of functional sodium channels.

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