On the mechanism by which phenytoin blocks post-tetanic potentiation at the frog neuromuscular junction

M. E. Selzer, Gavriel David, Y. Yaari

Research output: Contribution to journalArticle

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Abstract

Post-tetanic potentiation (PTP) was elicited at the frog sartorius and cutaneous pectoris neuromuscular junctions. A 30-sec, 30-Hz tetanus produced a 2- to 3-fold post-tetanic increase in endplate potential (EPP). In surface-recorded responses this PTP decayed in a double exponential way with time constants of 12.7 sec ± 2.4 (SEM) and 146.8 sec ± 36.6. In acute experiments 0.2 to 0.8 mM phenytoin (5,5-diphenylhydantoin, DPH) dramatically and reversibly reduced the early component. The late component was also reduced although to a lesser extent and often not reversibly. DPH reduced PTP even when there was no failure of the EPP during the tetanus. Thus, the DPH effect did not require a complete block of the presynaptic action potential. At longer exposures and higher DPH concentrations EPP failures did develop, and this was associated with a more profound suppression of PTP. PTP was also elicited in tetrodotoxin (TTX)-containing solutions using electronic stimulation of nerve terminals to elicit transmitter release. This PTP had a much shorter duration (about 30 sec) than that seen in normal Ringer's solution and was followed by depression of EPP amplitudes. Thus, sodium entry into nerve terminals enables a mechanism which greatly prolongs PTP. DPH had no effect on PTP in TTX. These results, together with others in the literature, suggest that the reduction of PTP by DPH involves a graded reduction of sodium influx into nerve terminals during high rates of axon stimulation. The development of all-or-none failures of the presynaptic action potential results in even greater suppression of PTP.

Original languageEnglish
Pages (from-to)2894-2899
Number of pages6
JournalJournal of Neuroscience
Volume5
Issue number11
StatePublished - Dec 1 1985
Externally publishedYes

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Neuromuscular Junction
Phenytoin
Anura
Tetrodotoxin
Tetanus
Action Potentials
Sodium
Axons
Skin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

On the mechanism by which phenytoin blocks post-tetanic potentiation at the frog neuromuscular junction. / Selzer, M. E.; David, Gavriel; Yaari, Y.

In: Journal of Neuroscience, Vol. 5, No. 11, 01.12.1985, p. 2894-2899.

Research output: Contribution to journalArticle

Selzer, M. E. ; David, Gavriel ; Yaari, Y. / On the mechanism by which phenytoin blocks post-tetanic potentiation at the frog neuromuscular junction. In: Journal of Neuroscience. 1985 ; Vol. 5, No. 11. pp. 2894-2899.
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