Advertisement

Neurophysiology

, Volume 28, Issue 4–5, pp 173–177 | Cite as

Effects of (±)-kavain on inactivation of voltage-operated Na+ channels

  • E. I. Magura
Article
  • 23 Downloads

Abstract

Effects of a kava-pyrone (±)-kavain on fast inactivation of Na+ channels were studied in experiments on isolated neurons from the rat hippocampus. (±)-Kavain was found to block Na+ channels, and its effect was voltage-dependent. At the holding potentials of −100 and −80 mV, IC50 for (±)-kavain was 744.9 and 178.8 µM, respectively. The inactivation characteristic of Na+ channels was satisfactorily described with the Boltzmann's equation both in the control and under (±)-kavain application. (±)-Kavain at a 330 µM concentration shifted theV1/2 toward more negative values by 14.4 mV and concurrently modified the slope factor: the latter was 5.7 mV in the control, while under the influence of 330 µM (±)-kavain it reached 6.7 mV. In agreement with Hille's hypothesis of a “modulated receptor,” inactivated Na+ channels demonstrated an increased sensitivity to kavain. (±)-Kavain effects resulted in an increase in the rate of depolarization-related fast inactivation, while the process of recovery from inactivation became slower when the membrane was hyperpolarized. Our data show that under the (±)-kavain effect the probability of the inactivated state of Na+ channels increases, and the state of fast inactivation is stabilized.

Keywords

Slope Factor Fast Inactivation Channel Increase Inactivation Characteristic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. Urenjak and T. P. Obrenovitch, “Pharmacological modulation of voltage-gated Na+ channels: a rational and effective strategy against ishemic brain damage,”Pharmacol. Rev.,48, No. 1, 21–67 (1996).Google Scholar
  2. 2.
    C. P. Taylor and B. S. Meldrum, “Na+-channels as targets for neuroprotective drugs,”,TIPS,16, 309–316 (1995).Google Scholar
  3. 3.
    H. J. Meyer, “Pharmacology of kava,” in:Ethnopharmacologic Search for Psychoactive Drugs, D. H. Efron, B. Holmstedt, and N. S. Kline (eds.), Raven Press, New York (1979), pp. 133–140.Google Scholar
  4. 4.
    V. Lebot, M. Merlin, and L. Lindstrom,Kava. The Pacific Drug, Yale Univ. Press, New Haven (1992).Google Scholar
  5. 5.
    Y. N. Singh, “Kava: an overview,”J. Ethnopharmacol.,37, 13–45 (1992).Google Scholar
  6. 6.
    J. Gleitz, A. Beile, and T. Peters, “(±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex,”Neuropharmacology,34, 1133–1138 (1995).Google Scholar
  7. 7.
    J. Gleitz, A. Beile, and T. Peters, “(±)-Kavain inhibits veratridine- and KCl-induced increase in intracellular Ca2+ and glutamate-release of rat cerebrocortical synaptosomes,”Neuropharmacology,35, 179–186 (1996).Google Scholar
  8. 8.
    D. Schmitz, C. L. Zhang, and S. S. Chatterjee, “Effects of methysticin on three different models of seizure-like events studied in rat hippocampal and entorhinal cortex slices,”Naunyn-Schmiedeberg's Arch. Pharmacol.,351, 348–355 (1995).Google Scholar
  9. 9.
    V. A. Panchenko, J. Pintor, A. Ya. Tsyndrenko, et al., “Diadenosine polyphosphates selectively potentiate N-type Ca2+-channels in rat central neurons,”Neuroscience,70, No. 2, 353–360 (1996).Google Scholar
  10. 10.
    O. A. Krishtal, S. M. Marchenko, and V. I. Pidoplichko, “Receptor for ATP in membrane of mammalian sensory neurones,”Neurosci. Lett.,35, 41–45 (1983).Google Scholar
  11. 11.
    N. I. Kiskin, I. V. Chizhmakov, A. Ya. Tsyndrenko, et al., “R56865 and flunarizine as Na+-channel blockers in isolated Purkinje neurons of rat cerebellum,”Neuroscience,54, No. 3, 575–585 (1993).Google Scholar
  12. 12.
    R. W. Tsien and D. Noble, “A transition state theory approach to the kinetics of conductance changes in excitable membranes,”J. Membrane Biol.,1, No. 2, 248–273 (1969).Google Scholar
  13. 13.
    A. L. Hodgkin and A. F. Huxley, “The dual effect of membrane potential on sodium conductance in the giant axon ofLoligo,”J. Physiol.,116, 497–506 (1952).Google Scholar
  14. 14.
    W. A. Catterall, “Common modes of drug action on Na+ channels: local anesthetics, anti-arrhythmics and anti-convulsants,”TIPS,8, 57–65 (1987).Google Scholar
  15. 15.
    C. Quan, W. M. Mok, and G. K. Wang, “Use-dependent inhibition of Na+ currents by benzocaine homologs,”Biophys. J.,70, Jan., 194–201 (1996).Google Scholar
  16. 16.
    J. Patlak, “Molecular kinetics of voltage-dependent Na+ channels,”Physiol. Rev.,71, 1047–1080 (1991).Google Scholar
  17. 17.
    J. C. McPhee, D. S. Ragsdale, T. Scheuer, and W. A. Catterall, “A critical role for transmembrane segment IVS6 of the sodium channelα subunit in fast inactivation,”J. Biol. Chem.,270, No. 20, 12025–12034 (1995).Google Scholar
  18. 18.
    C. M. Armstrong and F. Bezanilla, “Inactivation of the sodium channel. II. Gating current experiments,”J. Gen. Physiol.,70, 567–590 (1977).Google Scholar
  19. 19.
    F. Bezanilla and C. M. Armstrong, “Inactivation of the sodium channel. I. Sodium current experiments,”J. Gen. Physiol.,70, 549–566 (1977).Google Scholar
  20. 20.
    R. W. Aldrich, D. P. Corey, and C. F. Stevens, “A reinterpretation of mammalian sodium channel gating based on single channel recording,”Nature,306, 436–441 (1983).Google Scholar
  21. 21.
    L. Goldman and C. L. Schauf, “Inactivation if the sodium current inMyxicola giant axons: evidence for coupling to the activation process,”J. Gen. Physiol.,59, 659–675 (1972).Google Scholar
  22. 22.
    C. M. Armstrong, “Sodium channels and gating currents,”Physiol. Rev.,61, 644–683 (1981).Google Scholar
  23. 23.
    B. Hille, “Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction,”J. Gen. Physiol.,69, 497–515 (1977).Google Scholar
  24. 24.
    B. P. Bean, C. J. Cohen, and R. W. Tsien, “Lidocain block of cardiac sodium channels,”J. Gen. Physiol.,81, 613–642 (1983).Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • E. I. Magura
    • 1
  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKievUkraine

Personalised recommendations