著者

丸田 聡 山岡 薫 大越 夏実 山下 まり

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.49, pp.443-448, 2007-08-24

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Tetrodotoxin (TTX) and saxitoxin (STX) bind to a single site in the outer pore of the voltage-gated sodium channels (Na_vs), formed by the amino-acid residues in the outer-pore loops (p-loops) located between the S5 and S6 segments of each of the homologous domain (I-IV) of the a-subunit. Since puffer fish and newts accumulate TTX at high concentration in their tissues, they are thought to have special defense systems against their own TTX. We previously obtained a cDNA encoding Na_v from Fugu pardalis skeletal muscle (fMNa1=fNav1.4a). In fNav1.4a protein, the aromatic amino acid in p-loop region of Domain I in TTX-sensitive Nays was replaced by Asn. Also, Kaneko et al. reported that similar mutation was found in Na_v of retinal neuron of the newt, Cynops pyrrhogaster. In this study, we confirmed that these mutations are responsible to TTX-resistance of puffer fish and newts by evaluation of IC_<50>-TTX values of the corresponding mutants of rNav1.2a transiently expressed in HEK293 cells by electrophysiological study.