P-type calcium channels blocked by the spider toxin omega-Aga-IVA

Nature. 1992 Feb 27;355(6363):827-9. doi: 10.1038/355827a0.


Voltage-dependent calcium channels mediate calcium entry into neurons, which is crucial for many processes in the brain including synaptic transmission, dendritic spiking, gene expression and cell death. Many types of calcium channels exist in mammalian brains, but high-affinity blockers are available for only two types, L-type channels (targeted by nimodipine and other dihydropyridine channel blockers) and N-type channels (targeted by omega-conotoxin). In a search for new channel blockers, we have identified a peptide toxin from funnel web spider venom, omega-Aga-IVA, which is a potent inhibitor of both calcium entry into rat brain synaptosomes and of 'P-type' calcium channels in rat Purkinje neurons. omega-Aga-IVA will facilitate characterization of brain calcium channels resistant to existing channel blockers and may assist in the design of neuroprotective drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / physiology*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Molecular Sequence Data
  • Neurons / drug effects
  • Neurons / physiology*
  • Nitrendipine / pharmacology
  • Peptides, Cyclic / pharmacology
  • Rats
  • Spider Venoms / isolation & purification
  • Spider Venoms / pharmacology*
  • omega-Agatoxin IVA
  • omega-Conotoxins*


  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides, Cyclic
  • Spider Venoms
  • omega-Agatoxin IVA
  • omega-Conotoxins
  • Conus magus toxin
  • Nitrendipine