OMEGA-PHONETOXIN-IIA - A CALCIUM-CHANNEL BLOCKER FROM THE SPIDER PHONEUTRIA NIGRIVENTER

A peptide with neurotoxic effect on mammals, purified from the venom o f the spider Phoneutria nigriventer, was studied regarding its primary structure and its effects on voltage-gated calcium channels. The pept ide, named omega-phonetoxin-IIA, has 76 amino acids residues, with 14 Cys forming 7 disulphide bonds, and a molecular weight of 8362.7 Da. T he neurotoxicity is a consequence of the peptide's blocking effects on high-voltage-activated (HVA) calcium channels. N-type HVA calcium cha nnels of rat dorsal root ganglion neurons are blocked with affinity in the sub-nanomolar concentration range. The toxin also blocks L-type c hannels of rat beta pancreatic cells, with an affinity 40 times lower. Although not studied in detail, evidence indicates that the toxin als o blocks other types of HVA calcium channels, such as P and Q. No effe ct was observed on low-voltage-activated, T-type calcium channels. The significant homologies between omega-phonetoxin-IIA and the peptides of the omega-agatoxin-III family, and the overlapping inhibitory effec ts on calcium channels are discussed in terms of the structure-activit y relationship.