[omega]-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer

• Published in: Pflügers Archiv 1998-07, Vol.436 (4), p.545
• Main Authors: Cassola, Antonio Carlos, Jaffe, Howard, Fales, Henry M, Castro Afeche, Solange, Magnoli, Fabio, Cipolla-neto, José
• Format: Article
• Language: English
• Subjects: Calcium; Molecular weight; Peptides
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240050670

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