title: 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis.
abstract: This study investigated the effect of 3,4-diaminopyridine (3,4-DAP), a potent potentiator of transmitter release, on neuromuscular transmission in vivo in a mouse model of myasthenia gravis (MG) caused by antibodies against muscle-specific kinase (MuSK; MuSK-MG) and ex vivo in diaphragm muscle from these mice. 3,4-DAP significantly improved neuromuscular transmission, predominantly by increasing acetylcholine (ACh) release, supporting presynaptic potentiation as an effective treatment strategy for MuSK-MG patients who have defective transmitter release. In MuSK-MG, we suggest that only low-dose acetylcholinesterase (AChE) inhibitors be used to avoid side effects, and we propose that 3,4-DAP may be effective as a symptomatic therapy.
authors.affiliation: Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
authors.forename: Shuuichi
authors.initials: S
authors.lastname: Mori
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kishi
authors.forename: Sachiho
authors.initials: S
authors.lastname: Kubo
authors.forename: Takuyu
authors.initials: T
authors.lastname: Akiyoshi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Konishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shigemoto
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077770:Amifampridine; D000818:Animals; D001323:Autoantibodies / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000077770:Amifampridine