A Novel Hydrophobic ω-Conotoxin Blocks Molluscan Dihydropyridine-Sensitive Calcium Channels

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Abstract
A novel calcium channel blocking peptide designated ω-conotoxin-TxVII has been characterized from the venom of the molluscivorous snail Conus textile. The amino acid sequence (CKQADEPCDVFSLDCCTGICLGVCMW) reveals the characteristic cysteine framework of ω-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 δ-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 ω-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.