, Volume 30, Issue 4–5, pp 285–288 | Cite as

Kinetic characteristics of interaction of conotoxin with N-type Ca2+ channels in rat hippocampal neurons

  • A. I. Fisyunov
  • O. A. Krishtal
Poster Communications


The binding and unbinding constants describing interaction of ω-CTx-GVIA with N-type Ca2+ channels were calculated based on the time course of the blocking action of the toxin. The experiments were carried out on pyramidal neurons freshly dissociated from theCA3 region of the rat hippocampus using a “concentration-clamp” technique and a patch-clamp technique in the whole-cell configuration. The bindingk 1 and unbindingk −1 constants were evaluated as 0.32 (μM·sec)−1 and 0.004 sec−1, respectively. The dissociation constantK D kinetically derived from the ratiok −1/k 1 was 0.012 μM. These values allow us to interpret the apparent “irreversibility” of the toxin action.


Global Cerebral Ischemia Peripheral Neuron Simple Kinetic Model Toxin Molecule Chick Sensory Neurone 
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  1. 1.
    B. M. Olivera, J. M. McIntosh, L. J. Cruz, et al., “Purification and sequence of a presynaptic peptide toxin fromConus geographus venom,”Biochemistry,23, 5087–5090 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    E. W. McCleskey, A. P. Fox, D. H. Feldman, et al., “Ω-Conotoxin: Direct and persistent blockade of specific types of calcium channels in neurons but not in muscle,”Proc. Natl. Acad. Sci. USA,84, 4327–4331 (1987).PubMedCrossRefGoogle Scholar
  3. 3.
    L. J. Cruz and B. M. Olivera, “Calcium channel antagonists,”J. Biol. Chem.,261, 6230–6233 (1986).PubMedGoogle Scholar
  4. 4.
    A. P. Fox, M. C. Nowycky, and R. W. Tsien, “Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones”J. Physiol.,394, 149–172 (1987).PubMedGoogle Scholar
  5. 5.
    A. P. Fox, M. C. Nowycky, and R. W. Tsien, “Single-channel recordings of three types of calcium channels in chick sensory neurones,”J. Physiol.,394, 173–200 (1987).PubMedGoogle Scholar
  6. 6.
    D. H. Feldman, B. M. Olivera, and D. Yoshikami, “OmegaConus geographus toxin: a peptide that blocks calcium channels,”FEBS Lett.,214, 295–300 (1987).PubMedCrossRefGoogle Scholar
  7. 7.
    M. R. Plummer, D. E. Logothetis, and P. Hess, “Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons,”Neuron,2, 1453–1463 (1989).PubMedCrossRefGoogle Scholar
  8. 8.
    E. Carbone, E. Sher, and F. Clementi, “Ca2+ currents in human neuroblastoma IMR32 cells: kinetics, permeability and pharmacology,”Pflügers Arch.,416, 170–179 (1990).PubMedCrossRefGoogle Scholar
  9. 9.
    M. M. Usowicz, H. Porzig, C. Becker, and H. Reuter, “Differential expression by nerve growth factor of two types of Ca2+ channels in rat phaeochromocytoma cell lines,”J. Physiol.,426, 95–116 (1990).PubMedGoogle Scholar
  10. 10.
    L. J. Regan, D. W. Y. Sah, and B. P. Bean, “Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin,”Neuron,6, 269–280 (1981).CrossRefGoogle Scholar
  11. 11.
    K. L. Valentino, R. Newcomb, T. Gadbois, et al., “A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia,”Proc. Natl. Acad. Sci. USA,90, 7894–7897 (1993).PubMedCrossRefGoogle Scholar
  12. 12.
    A. Buchan, S. Z. Gertler, H. Li, et al., “A selective N-type Ca2+ channel blocker preventsCA1 injury 24 hours following severe forebrain ischemia and reduces infarction following focal ischemia,”J. Cerebr. Blood Flow Metab., Nov., Abstr.14:6, 903–910 (1994).Google Scholar
  13. 13.
    T. Singh, T. Gadbois, K. L. Valentino, et al., “24-hour infusion of SNX-111 protects against neuronal death after global cerebral ischemia with minimal adverse effects,”Soc. Neurosci. Abstr.,19, 850 (1993).Google Scholar
  14. 14.
    M. L. Smith and B. K. Siesjo, “Postischemia treatment with omega-conopeptide SNX-111 protects the rat brain against ischemic damage,” in:Pharmacology of Cerebral Ischemia, J. Krieglstein and H. Oberpilcher (eds.), Wissenschaftliche Verlag, Stuttgart (1992), pp. 161–167.Google Scholar
  15. 15.
    K. Yamada, S. Teraoka, T. Morita, et al., “ω-Conotoxin GVIA protects against ischemic-induced neuronal death in the Mongolian gerbil but not against quinolinic acid-induced neurotoxicity in the rat,”Neuropharmacology,33, 251–254 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    D. Xue, Z. G. Huang, K. Barnes, et al., “SNX-111 reduces neocortical infarction despite intra- and post-ischemic hypotension following focal ischemia,”Soc. Neurosci. Abstr.,19, 1643 (1993).Google Scholar
  17. 17.
    Q. Zhao, M. L. Smith, and B. K. Siesjo, “The omega-conopeptide SNX-111, an N-type calcium channel blocker, dramatically ameliorates brain damage due to transient focal ischemia,”Acta Physiol. Scand.,150, 459–461 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    S. Takizawa, K. Matsushima, Y. Shinohara, et al., “A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume,”J. Cerebr. Blood Flow Metab., Nov., Abstr. 14:6, 911–918 (1994).Google Scholar
  19. 19.
    I. V. Chizhmakov, N. I. Kiskin, and O. A. Krishtal, “Two types of N-methyl-D-aspartate receptor in isolated hippocampal neurons of rat,”J. Physiol.,448, 453–472 (1992).PubMedGoogle Scholar
  20. 20.
    J. R. Laura, W. Y. S. Dinah, and B. P. Been, “Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and ω-conotoxin,”Neuron,6, 269–280 (1991).CrossRefGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 1999

Authors and Affiliations

  • A. I. Fisyunov
    • 1
  • O. A. Krishtal
    • 1
  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKyivUkraine

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