Fainzilber M, Lodder J C, van der Schors R C, Li K W, Yu Z, Burlingame A L, Geraerts W P, Kits K S
Graduate School Neurosciences Amsterdam, Institute of Neuroscience, Vrije Universiteit, The Netherlands.
Biochemistry. 1996 Jul 2;35(26):8748-52. doi: 10.1021/bi9602674.
A novel calcium channel blocking peptide designated omega-conotoxin-Tx VII has been characterized from the venom of the molluscivorous snail Conus textile. The amino acid sequence (CKQADEPCDVFSLDCCTGICLGVCMW) reveals the characteristic cysteine framework of omega-conotoxins, but it is extremely hydrophobic for this pharmacological class of peptides and further unusual in its net negative charge (-3). It is further striking that the sequence of TxVII, a calcium current blocker, is 58% identical to that of delta-conotoxin-TxVIA, which targets sodium channels. TxVII effects were examined in the caudodorsal cell (CDC) neurons from the mollusc Lymnaea stagnalis. The toxin has no significant effect on sodium or potassium currents in these cells, but it clearly blocks the calcium currents. TxVII most prominently blocks the slowly inactivating, dihydropyridine- (DHP-) sensitive current in CDCs, while blockade of the rapidly inactivating current is less efficient. This novel omega-conotoxin is apparently targeted to DHP-sensitive calcium channels and thereby provides a lead for future design of selective conopeptide probes for L-type channels.
一种名为ω-芋螺毒素-Tx VII的新型钙通道阻断肽已从食螺蜗牛织锦芋螺的毒液中得到鉴定。其氨基酸序列（CKQADEPCDVFSLDCCTGICLGVCMW）显示出ω-芋螺毒素特有的半胱氨酸框架，但对于这类药理活性肽而言，它具有极强的疏水性，且净电荷为-3，这一点尤为罕见。更值得注意的是，作为一种钙电流阻断剂的TxVII的序列与靶向钠通道的δ-芋螺毒素-TxVIA的序列有58%的同源性。在椎实螺的尾背细胞（CDC）神经元中检测了TxVII的作用。该毒素对这些细胞中的钠电流或钾电流没有显著影响，但能明显阻断钙电流。TxVII最显著地阻断了CDC中缓慢失活的、对二氢吡啶（DHP）敏感的电流，而对快速失活电流的阻断效率较低。这种新型的ω-芋螺毒素显然作用于对DHP敏感的钙通道，从而为未来设计针对L型通道的选择性芋螺肽探针提供了线索。
