Toxityping rat brain calcium channels with omega-toxins from spider and cone snail venoms

Biochemistry. 1993 Nov 30;32(47):12566-70. doi: 10.1021/bi00210a003.


Different types of voltage-sensitive Ca2+ channels in the brain can be defined by specific ligands: L-type Ca2+ channels are uniquely sensitive to dihydropyridines, and N-type Ca2+ channels are selectively blocked by the Conus peptide omega-CTX-GVIA. Cloning data have revealed additional calcium channel types in mammalian brain for which selective ligands would be desirable. We describe binding experiments involving three newer ligands that block dihydropyridine- and omega-CTX-GVIA-resistant Ca channels: omega-Aga-IIIA and omega-Aga-IVA from venom of the spider Agelenopsis aperta and omega-CTX-MVIIC from Conus magus. [125I]omega-Aga-IVA binds with high affinity (IC50 = approximately 50 nM) to receptors in rat brain which may correspond to P-like calcium channels. A second high-affinity site (IC50 = approximately 1 nM) is defined by [125I]omega-CTX-MVIIC, proposed here to be on an "O"-type calcium channel. [125I]omega-Aga-IIIA targets homologous binding sites present on multiple Ca channel types. The IIIA sites overlap with the binding sites for [125I]omega-CTX-GVIA and [125I]omega-CTX-MVIIC. The IIIA sites do not overlap with the site defined by omega-Aga-IVA. Thus toxin ligands may be highly specific for a particular Ca channel (i.e., GVIA for the N-type channel) or exhibit broader specificity (i.e., omega-Aga-IIIA, which appears to bind L-, N-, P-, and O-type Ca2+ channels).

Publication types

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

MeSH terms

  • Agatoxins
  • Animals
  • Brain / metabolism
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / classification*
  • Calcium Channels / drug effects
  • Iodine Radioisotopes
  • Ligands
  • Mollusk Venoms / pharmacology*
  • Peptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Snails
  • Spider Venoms / isolation & purification
  • Spider Venoms / pharmacology*
  • Spiders
  • Synaptosomes / metabolism
  • omega-Agatoxin IVA
  • omega-Conotoxins*


  • Agatoxins
  • Calcium Channel Blockers
  • Calcium Channels
  • Iodine Radioisotopes
  • Ligands
  • Mollusk Venoms
  • Peptides
  • Spider Venoms
  • omega-Agatoxin IVA
  • omega-Conotoxins
  • omega-agatoxin III
  • omega-conotoxin-MVIIC
  • Calcium