title: Effect of 3,4-diaminopyridine at the murine neuromuscular junction.
abstract: 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.
  
  
  
  Quantal release of acetylcholine was studied in diaphragm muscles of mice, using in vitro intracellular microelectrode recordings.
  
  
  
  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.
  
  
  
  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. Muscle Nerve, 2016 Muscle Nerve 55: 223-231, 2017.
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Ng
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Lee
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Schrumpf
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Mazurek
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lee Lo
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Sharleen K
authors.initials: SK
authors.lastname: Gill
authors.affiliation: University of California, Davis School of Medicine Department of Neurology, University of California Davis, Davis, California, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Maselli
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009469:Neuromuscular Junction / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000081:Acetamides; D026902:Potassium Channel Blockers; C030686:acetamide; D015761:4-Aminopyridine; D000077770:Amifampridine; D002118:Calcium
keywords: 3,4-diaminopyridine; Lambert-Eaton myasthenic syndrome; congenital myasthenic syndromes; endplate potential; neuromuscular junction; quantal release