Frequency-dependent effects of phenytoin on frog junctional transmission

Presynaptic mechanisms

Yoel Yaari, Michael E. Selzer, Gavriel David

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The action of the antiepileptic drug, phenytoin, on junctional transmission at various frequencies of synaptic activation was studied in frog nerve-muscle preparations. Intracellular recordings were made from muscle end-plates, and extracellular focal and subendothelial recordings were obtained from motor nerve terminals and their parent axons, respectively. When the motor nerve was stimulated at 100-200 Hz, exposure to the drug (0.1-0.3 mM) induced intermittent failures of junctional transmission which appeared faster as the rate of stimulation was increased. At these and at lower stimulation frequencies (30-50 Hz), in which failures of transmission occurred only rarely, phenytoin markedly limited the buildup of end-plate potential amplitude during the period of repetitive nerve stimulation (tetanic potentiation). Several lines of evidence suggest that both drug effects are consequent to a frequency-dependent depression of the action potential at motor axons and terminals, which could lead to an intermittent conduction block at the higher rates of stimulation. The selective action of phenytoin on high frequency synaptic transmission may contribute to the specificity shown by this drug in suppressing epileptic seizures while sparing normal neuronal activity.

Original languageEnglish
Pages (from-to)102-110
Number of pages9
JournalBrain Research
Volume345
Issue number1
DOIs
StatePublished - Oct 14 1985
Externally publishedYes

Fingerprint

Phenytoin
Anura
Pharmaceutical Preparations
Neuromuscular Junction
Excitatory Postsynaptic Potentials
Presynaptic Terminals
Synaptic Transmission
Anticonvulsants
Action Potentials
Axons
Epilepsy
Muscles

Keywords

  • antiepileptic
  • frequency-dependent
  • frog
  • neuromuscular junction
  • phenytoin
  • presynaptic mechanism
  • tetanic potentiation

ASJC Scopus subject areas

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

Cite this

Frequency-dependent effects of phenytoin on frog junctional transmission : Presynaptic mechanisms. / Yaari, Yoel; Selzer, Michael E.; David, Gavriel.

In: Brain Research, Vol. 345, No. 1, 14.10.1985, p. 102-110.

Research output: Contribution to journalArticle

Yaari, Yoel ; Selzer, Michael E. ; David, Gavriel. / Frequency-dependent effects of phenytoin on frog junctional transmission : Presynaptic mechanisms. In: Brain Research. 1985 ; Vol. 345, No. 1. pp. 102-110.
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