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, 2013. Copyright © 2013 Wiley Periodicals, Inc.

Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor / Deflorio, Cristina; Catalano, Myriam; Fucile, Sergio; Limatola, Cristina; Grassi, Francesca. - In: MUSCLE & NERVE. - ISSN 0148-639X. - STAMPA. - 49:(2014), pp. 90-97. [10.1002/mus.23870]

Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor.

DEFLORIO, Cristina;CATALANO, Myriam;FUCILE, Sergio;LIMATOLA, Cristina;GRASSI, Francesca
2014

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 (2-10 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, 2013. Copyright © 2013 Wiley Periodicals, Inc.
2014
congenital myasthenic syndrome
01 Pubblicazione su rivista::01a Articolo in rivista
Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate acetylcholine receptor / Deflorio, Cristina; Catalano, Myriam; Fucile, Sergio; Limatola, Cristina; Grassi, Francesca. - In: MUSCLE & NERVE. - ISSN 0148-639X. - STAMPA. - 49:(2014), pp. 90-97. [10.1002/mus.23870]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/523268
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