Frequency-dependent action of phenytoin on lamprey spinal axons

Elizabeth M. Adler, Yoel Yaari, Gaby David, Michael E. Selzer

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The effect of the antiepileptic drug phenytoin (diphenylhydantoin, DPH) was tested on the conduction of intracellularly recorded action potentials in lamprey giant reticulospinal axons. When the isolated spinal cord was exposed to 80 μM DPH for up to 4 h, no significant effect was seen on the amplitude or conduction velocity of the action potential, although the maximum rate of rise was reduced from 247.8 to 149.6 V/s after 1 h. However, at higher stimulus frequencies both the amplitude and conduction velocity of the action potential were reduced progressively during a 500 stimulus train. The reduction was greater the higher the stimulus frequency, and was reversed upon return to 1 Hz stimulation. At frequencies greater than 40 Hz an all-or-none block developed. This also developed sooner the higher the stimulus frequency. Axons bathed in drug-free solutions did not show this effect at stimulus frequencies up to 100 Hz. Similar effects were seen in 16 μM DPH when the spinal cord was exposed to the drug overnight. This is close to the human therapeutic CSF level. The frequency-dependent depression of the action potential was greatly potentiated by increasing the extracellular potassium concentration from 2.1 to 5 mM. Under these conditions the axons rapidly developed block at stimulus frequencies as low as 2 Hz, and this was not reversible during a 5 h wash. In the absence of DPH, 5 mM potassium produced a 4-5 mV depolarization, but did not induce a frequency-dependent block. This effect of potassium may be important to the therapeutic effect of DPH because during epileptiform activity the extracellular K+ increases several fold.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalBrain Research
Volume362
Issue number2
DOIs
StatePublished - Jan 8 1986

Keywords

  • action potential
  • axon
  • frequency-dependence
  • lamprey
  • phenytoin
  • potassium
  • spinal cord

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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    Adler, E. M., Yaari, Y., David, G., & Selzer, M. E. (1986). Frequency-dependent action of phenytoin on lamprey spinal axons. Brain Research, 362(2), 271-280. https://doi.org/10.1016/0006-8993(86)90451-8