This work was supported by a grant from Association Française contre les Myopathies to FG. C.D. was supported by the PhD Program in Neurophysiology at Sapienza University, Rome. The Authors declare no conflict of interests.
Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor
Article first published online: 15 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Muscle & Nerve
Volume 49, Issue 1, pages 90–97, January 2014
How to Cite
Deflorio, C., Catalano, M., Fucile, S., Limatola, C. and Grassi, F. (2014), Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor. Muscle Nerve, 49: 90–97. doi: 10.1002/mus.23870
- Issue published online: 16 DEC 2013
- Article first published online: 15 JUL 2013
- Accepted manuscript online: 5 APR 2013 03:40AM EST
- Manuscript Accepted: 29 MAR 2013
- Congenital myasthenic syndrome;
- Nicotinic acetylcholine receptor;
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 (2–10 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. Muscle Nerve 49: 90–97, 2014