Fainzilber M, Kofman O, Zlotkin E, Gordon D
Department of Cell and Animal Biology, Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
J Biol Chem. 1994 Jan 28;269(4):2574-80.
The peptide conotoxin TxVIA is selectively toxic to molluscs and slows sodium current inactivation in mollusc neurons. Here we show that TxVIA binds with high affinity to new sites on sodium channels in both mollusc and rat central nervous systems, despite its lack of toxicity to vertebrates. Furthermore, TxVIA protects from the toxic effects of Conus striatus toxin in rat brain. The TxVIA binding site differs from other neurotoxin receptor sites affecting sodium channel inactivation in that binding is not voltage-dependent and undergoes negative allosteric modulation by veratridine. TxVIA therefore represents a novel category of sodium channel probes, designated delta-conotoxins. TxVIA is shown to discriminate between sodium channels in different phyla by activity but not by binding, thus providing a lead for the study of structural elements affecting gating modes of sodium channels.
肽类芋螺毒素TxVIA对软体动物具有选择性毒性，并能减缓软体动物神经元中的钠电流失活。我们在此表明，尽管TxVIA对脊椎动物无毒，但它能以高亲和力与软体动物和大鼠中枢神经系统中钠通道的新位点结合。此外，TxVIA可保护大鼠大脑免受带纹芋螺毒素的毒性作用。TxVIA结合位点与其他影响钠通道失活的神经毒素受体位点不同，其结合不依赖电压，并受到藜芦碱的负变构调节。因此，TxVIA代表了一类新型的钠通道探针，称为δ-芋螺毒素。研究表明，TxVIA可通过活性而非结合来区分不同门的钠通道，从而为研究影响钠通道门控模式的结构元件提供了线索。
