Home LiteratureArticle Details
PMID: 1713686 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of N- and L-type Ca2+ channels by the spider venom toxin omega-Aga-IIIA.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 15 ·1991-08-01 ·Pages 6628-31

Mintz IM, Venema VJ, Adams ME, Bean BP

Abstract

omega-Aga-IIIA, an 8.5-kDa peptide toxin isolated from the venom of Agelenopsis aperta, was found to be a highly potent inhibitor of Ca channels in cardiac muscle and in peripheral and central neurons of rats and frogs. Cardiac L-type Ca channels were completely (Kd approximately 0.6 nM) blocked by omega-Aga-IIIA. In sensory neurons, the toxin inhibited most high-threshold Ca current but not T-type Ca current. omega-Aga-IIIA blocked with similar potency (Kd approximately 1.5 nM) both omega-conotoxin GVIA-sensitive and dihydropyridine-sensitive current components but left a fraction (approximately 35%) of high-threshold current that was also resistant to omega-conotoxin and dihydropyridines. The toxin blocks N- and L-type channels with equal potency and therefore may identify a high-affinity binding site common to these two Ca channel types.

MeSH Terms
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology Agatoxins Animals Calcium Channel Blockers/pharmacology Calcium Channels/drug effects,physiology Ganglia, Spinal/physiology Ganglia, Sympathetic/physiology Hippocampus/physiology In Vitro Techniques Muscles/physiology Neurons/physiology Peptides, Cyclic/pharmacology Rana catesbeiana Rats Spider Venoms/pharmacology omega-Conotoxin GVIA
Chemicals
Agatoxins Calcium Channel Blockers Calcium Channels Peptides, Cyclic Spider Venoms omega-agatoxin III 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester omega-Conotoxin GVIA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mintz I M
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Venema V J
Adams M E
Bean B P
References (27)
27 references, click to expand
  1. Classes of calcium channels in vertebrate cells.
    Annu Rev Physiol. 1989;51:367-84 PMID: 2540697
  2. Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1689-93 PMID: 2537980
  3. omega-Aga-I: a presynaptic calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.
    J Neurobiol. 1989 Jun;20(4):171-88 PMID: 2787835
  4. The agonist effect of dihydropyridines on Ca channels.
    Nature. 1984 Oct 11-17;311(5986):570-2 PMID: 6207438
  5. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists.
    Nature. 1984 Oct 11-17;311(5986):538-44 PMID: 6207437
  6. Primary culture of identified neurons from the visual cortex of postnatal rats.
    J Neurosci. 1986 Oct;6(10):3044-60 PMID: 3760948
  7. Peptide neurotoxins from fish-hunting cone snails.
    Science. 1985 Dec 20;230(4732):1338-43 PMID: 4071055
  8. Ca currents in human neuroblastoma IMR32 cells: kinetics, permeability and pharmacology.
    Pflugers Arch. 1990 Apr;416(1-2):170-9 PMID: 1693767
  9. ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics.
    J Neurosci. 1990 Jan;10(1):1-10 PMID: 1688928
  10. Funnel-web spider venom and a toxin fraction block calcium current expressed from rat brain mRNA in Xenopus oocytes.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4538-42 PMID: 2162047
  11. Calcium channels in vertebrate cells.
    Annu Rev Neurosci. 1990;13:337-56 PMID: 2158265
  12. Molecular properties of calcium channels.
    Rev Physiol Biochem Pharmacol. 1990;114:1-105 PMID: 2155469
  13. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration.
    J Physiol. 1967 Sep;192(2):479-92 PMID: 6050160
  14. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.
    J Physiol. 1987 Dec;394:149-72 PMID: 2451016
  15. Characterization of two kinds of high-voltage-activated Ca-channel currents in chick sensory neurons. Differential sensitivity to dihydropyridines and omega-conotoxin GVIA.
    Pflugers Arch. 1989 Jun;414(2):150-6 PMID: 2547195
  16. Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons.
    Neuron. 1989 May;2(5):1453-63 PMID: 2560643
  17. Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle.
    Proc Natl Acad Sci U S A. 1987 Jun;84(12):4327-31 PMID: 2438698
  18. Spider toxins selectively block calcium currents in Drosophila.
    Neuron. 1989 Dec;3(6):767-72 PMID: 2642017
  19. Neurotoxins from Plectreurys spider venom are potent presynaptic blockers in Drosophila.
    J Neurosci. 1987 Dec;7(12):4195-200 PMID: 2826721
  20. Identification and purification of an irreversible presynaptic neurotoxin from the venom of the spider Hololena curta.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3506-10 PMID: 3033650
  21. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates.
    Am J Physiol. 1985 Nov;249(5 Pt 2):H1056-60 PMID: 2998207
  22. Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin.
    Neuron. 1991 Feb;6(2):269-80 PMID: 1847065
  23. Single-channel recordings of three types of calcium channels in chick sensory neurones.
    J Physiol. 1987 Dec;394:173-200 PMID: 2451017
  24. Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology.
    J Gen Physiol. 1989 Jul;94(1):151-67 PMID: 2478659
  25. Multiple types of neuronal calcium channels and their selective modulation.
    Trends Neurosci. 1988 Oct;11(10):431-8 PMID: 2469160
  26. Long-opening mode of gating of neuronal calcium channels and its promotion by the dihydropyridine calcium agonist Bay K 8644.
    Proc Natl Acad Sci U S A. 1985 Apr;82(7):2178-82 PMID: 2580308
  27. Spider toxins: recent applications in neurobiology.
    Annu Rev Neurosci. 1989;12:405-14 PMID: 2648955
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.15.6628
Published
1991-08-01
Pages
6628-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52141
Subset
IM
Grants
NHLBI NIH HHS · HL 35034 · United States
NINDS NIH HHS · NS 02253 · United States
NINDS NIH HHS · NS 24472 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.15.6628 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2