Abstract
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 language | English |
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Pages (from-to) | 90-97 |
Number of pages | 8 |
Journal | Muscle and Nerve |
Volume | 49 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2014 |
Keywords
- Congenital myasthenic syndrome
- Endplate
- Excitotoxicity
- Fluoxetine
- Nicotinic acetylcholine receptor
- Patch-clamp
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)
- Physiology