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Pflügers Archiv

, Volume 436, Issue 4, pp 545–552 | Cite as

ω-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer

  • Antonio Carlos Cassola
  • Howard Jaffe
  • Henry M. Fales
  • Solange Castro Afeche
  • Fabio Magnoli
  • José Cipolla-Neto
Original Article

Abstract

 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.

Key words Calcium channel High-voltage-activated calcium channel ω-Phonetoxin-IIA Spider toxins L-Type calcium channel N-Type calcium channel 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Antonio Carlos Cassola
    • 1
  • Howard Jaffe
    • 2
  • Henry M. Fales
    • 3
  • Solange Castro Afeche
    • 4
  • Fabio Magnoli
    • 5
  • José Cipolla-Neto
    • 1
  1. 1.Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes, 1524, São Paulo, SP-05508-900, BrazilBR
  2. 2.LNC-NINDS Protein/Peptide Sequencing Facility, Basic Neurosciences Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD-20892, USAUS
  3. 3.Laboratory of Biophysical Chemistry, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, MD-20892, USAUS
  4. 4.Laboratory of Pharmacology, Butantan Institute, São Paulo, BrazilBR
  5. 5.Laboratory of Imunochemistry, Butantan Institute, São Paulo, BrazilBR

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