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A single serine residue confers tetrodotoxin insensitivity on the rat sensory‐neuron‐specific sodium channel SNS
Author(s) -
Sivilotti L,
Okuse K,
Akopian A.N,
Moss S,
Wood J.N
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00479-1
Subject(s) - sodium channel , tetrodotoxin , chemistry , sensory system , serine , neuron , neuroscience , sodium , nav1 , residue (chemistry) , biophysics , biochemistry , biology , enzyme , organic chemistry
Sensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC 50 =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 IC 50 s 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.