A single serine residue confers tetrodotoxin insensitivity on the rat sensory‐neuron‐specific sodium channel SNS

FEBS Letters

Akopian, A.N²  Wood, J.N²  Sivilotti, L²  Okuse, K²  Moss, S¹ 

[1] MRC Laboratory for Molecular Biology, University College London, Gower Street, London WC1 8LS, UK;Departments of Anatomy and Developmental Biology, University College London, Gower Street, London WC1 8LS, UK

关键词: Dorsal root ganglion;    Tetrodotoxin;    Saxitoxin;    Mutagenesis;    Sodium channel;    SNS;    sensory-neuron sodium channel;    TTX;    tetrodotoxin;    STX;    saxitoxin;    VGSCs;    voltage-gated sodium channels;    DRG;    dorsal root ganglia;   

DOI  :  10.1016/S0014-5793(97)00479-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Sensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC₅₀=60 μM). SNS is 65% homologous to the cardiac sodium channel, in which a single hydrophilic residue in the SS2 segment is critical for tetrodotoxin resistance. By site-directed mutagenesis, we have substituted phenylalanine for serine at the equivalent position in SNS: this mutated (S356F) SNS channel is functionally similar to wild-type SNS when expressed in Xenopus oocytes, but is potently blocked by tetrodotoxin and saxitoxin with IC₅₀s of 2.8 nM and 8.2 nM, respectively. These data provide clues to the rational design of selective blockers of SNS with potential as analgesic drugs.

【 授权许可】

Unknown