Nicotinic AChR in congenital myasthenic syndromes

Francesca Grassi, Sergio Fucile

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

About 20 % of the identified cases of congenital myasthenic syndromes are due to defects causing overstimulation of endplate ACh receptors, with consequent excessive Ca2+entry, endplate structural damage, and impairment of the neuromuscular transmission. Overstimulation arises from extended dwelling of ACh in the synaptic cleft because of absence of acetylcholine esterase or from prolonged activation of “slow-channel” mutant ACh receptors. The high Ca2+permeability of human endplate ACh receptor, recently described, likely predisposes to excitotoxic damage. The good knowledge of ACh receptor function has allowed molecular understanding of the defects introduced in channel kinetics and Ca2+permeability by slow-channel mutations and the design of efficient therapeutic strategies. These forms of congenital myasthenic syndrome are treated by limiting ACh-induced cation entry, thus preventing endplate degeneration. Several molecules of wide clinical use, such as fluoxetine and quinidine, but also verapamil and salbutamol modulate ACh receptor kinetics and ion selectivity and may be used to lower ACh-evoked responses in these patients. In this contribution we summarize the main findings in the field.

Original languageEnglish
Title of host publicationPathologies of Calcium Channels
PublisherSpringer Berlin Heidelberg
Pages695-711
Number of pages17
ISBN (Print)9783642402821, 9783642402814
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

Congenital Myasthenic Syndromes
Cholinergic Receptors
Permeability
Albuterol
Fluoxetine
Esterases
Acetylcholine
Cations
Ions
Mutation

Keywords

  • Acetylcholine
  • Congenital myasthenic syndromes
  • Nicotinic receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Grassi, F., & Fucile, S. (2014). Nicotinic AChR in congenital myasthenic syndromes. In Pathologies of Calcium Channels (pp. 695-711). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_33

Nicotinic AChR in congenital myasthenic syndromes. / Grassi, Francesca; Fucile, Sergio.

Pathologies of Calcium Channels. Springer Berlin Heidelberg, 2014. p. 695-711.

Research output: Chapter in Book/Report/Conference proceedingChapter

Grassi, F & Fucile, S 2014, Nicotinic AChR in congenital myasthenic syndromes. in Pathologies of Calcium Channels. Springer Berlin Heidelberg, pp. 695-711. https://doi.org/10.1007/978-3-642-40282-1_33
Grassi F, Fucile S. Nicotinic AChR in congenital myasthenic syndromes. In Pathologies of Calcium Channels. Springer Berlin Heidelberg. 2014. p. 695-711 https://doi.org/10.1007/978-3-642-40282-1_33
Grassi, Francesca ; Fucile, Sergio. / Nicotinic AChR in congenital myasthenic syndromes. Pathologies of Calcium Channels. Springer Berlin Heidelberg, 2014. pp. 695-711
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