Abstract
The effects of a synthetic 5,6-dihydro-alpha-kava-pyrone (+)-methysticin on voltage-operated Na+ channels was studied in isolated whole-cell patch-clampedCA1 hippocampal neurons. Within a concentration range of 1–400 µM, (+)-methysticin induced a rapid and partly reversible dose-dependent reduction of the peak amplitude of Na+ current. Shifts of the holding membrane potential toward more positive values considerably enhanced the blocking effect. The efficiency of this block showed no dependence on the frequency of stimulation. In addition, (+)-methysticin shifted a steady-state inactivation curve toward more negative membrane potentials, accelerated the time course of fast inactivation, and slowed down the recovery from inactivation. From the above findings, the voltage dependence of (+)-methysticin effect can be accounted for by an increased portion of inactivated Na+ channels. Thus, the effect of (+)-methysticin on voltage-operated Na+ channels is associated with decreased excitability of nerve cell membranes. This suggests that this drug is capable of suppressing seizure activity of different genesis, including epileptic seizures. More effective action of (+)-methysticin on depolarized neuronal membrane prompts its possible application for therapeutic purposes in pathological disorders accompanied by depolarization of neurons in damaged foci, in particular in the case of cerebral ischemia.
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Neirofiziologiya/Neurophysiology, Vol. 28, No. 4/5, pp. 179–185, July–October, 1996.
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Magura, E.I., Ostrovskaya, O.I., Kopanitsa, M.V. et al. Down-modulation induced block of voltage-operated Na+ channels in ratCA1 hippocampal neurons by (+)-methysticin. Neurophysiology 28, 140–144 (1996). https://doi.org/10.1007/BF02262775
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DOI: https://doi.org/10.1007/BF02262775