Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor

Cristina Deflorio, Myriam Catalano, Sergio Fucile, Cristina Limatola, Francesca Grassi

Research output: Contribution to journalArticlepeer-review


Introduction: 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 (2-10μM) 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.

Original languageEnglish
Pages (from-to)90-97
Number of pages8
JournalMuscle and Nerve
Issue number1
Publication statusPublished - Jan 2014


  • Congenital myasthenic syndrome
  • Endplate
  • Excitotoxicity
  • Fluoxetine
  • Nicotinic acetylcholine receptor
  • Patch-clamp

ASJC Scopus subject areas

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


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