Effect of 3,4-diaminopyridine at the murine neuromuscular junction

Fiona Ng, Diana C. Lee, Leah A. Schrumpf, Mary E. Mazurek, Victoria Lee Lo, Sharleen K. Gill, Ricardo A Maselli

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Introduction: We investigated the effects of 3,4-diaminopyridine (3,4-DAP) and its acetylated metabolite, N-(4-amino-pyridin-3-yl) acetamide (3-Ac), at the mammalian neuromuscular junction. Methods: Quantal release of acetylcholine was studied in diaphragm muscles of mice, using in vitro intracellular microelectrode recordings. Results: Under conditions of low probability of release, 3,4-DAP produced a 1,000% increase in quantal release, but 3-Ac had no effect. Under conditions of normal probability of release, the effect of 3,4-DAP was modest and limited by concurrent depletion of synaptic vesicles, especially with high concentrations of 3,4-DAP and high frequencies of nerve stimulation. Conclusions: These findings predict 3,4-DAP is most effective in conditions with low probability of quantal release, such as Lambert-Eaton myasthenic syndrome. A beneficial effect is also expected in disorders of neuromuscular transmission in which the effect of 3,4-DAP on quantal release is not limited by depletion of synaptic vesicles, such as postsynaptic congenital myasthenic syndromes.

Original languageEnglish (US)
JournalMuscle and Nerve
DOIs
StateAccepted/In press - 2016

Keywords

  • 3,4-diaminopyridine
  • Congenital myasthenic syndromes
  • Endplate potential
  • Lambert-Eaton myasthenic syndrome
  • Neuromuscular junction
  • Quantal release

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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    Ng, F., Lee, D. C., Schrumpf, L. A., Mazurek, M. E., Lee Lo, V., Gill, S. K., & Maselli, R. A. (Accepted/In press). Effect of 3,4-diaminopyridine at the murine neuromuscular junction. Muscle and Nerve. https://doi.org/10.1002/mus.25208