Sivilotti L, Okuse K, Akopian A N, Moss S, Wood J N
Department of Anatomy, University College London, UK.
FEBS Lett. 1997 Jun 2;409(1):49-52. doi: 10.1016/s0014-5793(97)00479-1.
Sensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC50 = 60 microM). 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.
感觉神经元表达一种对河豚毒素阻断具有高度抗性的钠通道（SNS，IC50 = 60微摩尔）。SNS与心脏钠通道有65%的同源性，其中SS2片段中的单个亲水残基对河豚毒素抗性至关重要。通过定点诱变，我们在SNS的等效位置用苯丙氨酸取代了丝氨酸：这种突变的（S356F）SNS通道在非洲爪蟾卵母细胞中表达时功能上与野生型SNS相似，但被河豚毒素和石房蛤毒素有效阻断，IC50分别为2.8纳摩尔和8.2纳摩尔。这些数据为合理设计具有潜在镇痛药物作用的SNS选择性阻滞剂提供了线索。
