A NOVEL HYDROPHOBIC OMEGA-CONOTOXIN BLOCKS MOLLUSCAN DIHYDROPYRIDINE-SENSITIVE CALCIUM-CHANNEL

A novel calcium channel blocking peptide designated omega-conotoxin-Tx VII has been characterized from the venom of the molluscivorous snail Conns textile. The amino acid sequence (CKQADEPCDVFSLDCCTGICLGVCMW) re veals the characteristic cysteine framework of omega-conotoxins, but i t is extremely hydrophobic for this pharmacological class of peptides and further unusual in its net negative charge (-3), It is further str iking that the sequence of TxVII, a calcium current blocker, is 58% id entical to that of delta-conotoxin-TxVIA, which targets sodium channel s. TxVII effects were examined in the caudodorsal cell (CDC) neurons f rom 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 inacti vating, dihydropyridine- (DHP-) sensitive current in CDCs: while block ade of the rapidly inactivating current is less efficient. This novel omega-conotoxin is apparently targeted to DHP-sensitive calcium channe ls and thereby provides a lead fur future design of selective conopept ide probes for L-type channels.