title: Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor.
abstract: BACKGROUND
  Fluoxetine is an open channel blocker of fetal muscle acetylcholine (ACh) receptor (AChR) and slow-channel mutant AChRs. It is used commonly to treat patients with slow-channel congenital myasthenic syndromes. Fluoxetine effects on adult wild-type endplate AChR are less characterized, although muscle AChR isoforms are differentially modulated by some drugs.
  
  
  METHODS
  Excitotoxicity assays and patch clamp recordings were performed in human embryonic kidney 293 (HEK) cells expressing wild-type or slow-channel mutant human AChRs.
  
  
  RESULTS
  Fluoxetine (2-10 μM) abolished ACh-induced death and decreased ACh-activated whole-cell currents in cells expressing all AChR types. In outside-out patches, fluoxetine rapidly curtailed ACh evoked unitary activity and macroscopic currents. The effect was increased if fluoxetine was applied before ACh.
  
  
  CONCLUSIONS
  Fluoxetine is an open channel blocker, but it also affects AChR in the closed state. AChR blockade likely underlies the rescue of HEK cells from ACh-induced death.
authors.affiliation: Fondazione Cenci Bolognetti, Dipartimento di Fisiologia e Farmacologia, Università Sapienza, Piazzale Aldo Moro 5, I-00185, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Deflorio
authors.forename: Myriam
authors.initials: M
authors.lastname: Catalano
authors.forename: Sergio
authors.initials: S
authors.lastname: Fucile
authors.forename: Cristina
authors.initials: C
authors.lastname: Limatola
authors.forename: Francesca
authors.initials: F
authors.lastname: Grassi
mesh_terms: D000109:Acetylcholine / Q000009:adverse effects* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005473:Fluoxetine / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D009045:Motor Endplate / Q000187:drug effects* / Q000502:physiology; D020294:Myasthenic Syndromes, Congenital / Q000503:physiopathology; D009498:Neurotoxins / Q000009:adverse effects* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D000109:Acetylcholine; D005473:Fluoxetine; D009498:Neurotoxins; D011950:Receptors, Cholinergic; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Congenital myasthenic syndrome; Endplate; Excitotoxicity; Fluoxetine; Nicotinic acetylcholine receptor; Patch-clamp