ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease.
Chloride currents
ClC-2 channels
PACAP
Patch-clamp
PolyQ-AR cells
Spinal and bulbar muscular atrophy (SBMA)
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
18
05
2020
accepted:
14
08
2020
pubmed:
29
8
2020
medline:
5
10
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by expansions of a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is associated with the progressive loss of lower motor neurons, together with muscle weakness and atrophy. PolyQ-AR is converted to a toxic species upon binding to its natural ligands, testosterone, and dihydrotestosterone (DHT). Our previous patch-clamp studies on a motor neuron-derived cell model of SBMA showed alterations in voltage-gated ion currents. Here, we identified and characterized chloride currents most likely belonging to the chloride channel-2 (ClC-2) subfamily, which showed significantly increased amplitudes in the SBMA cells. The treatment with the pituitary adenylyl cyclase-activating polypeptide (PACAP), a neuropeptide with a proven protective effect in a mouse model of SBMA, recovered chloride channel current alterations in SBMA cells. These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease.
Identifiants
pubmed: 32856205
doi: 10.1007/s12031-020-01687-5
pii: 10.1007/s12031-020-01687-5
doi:
Substances chimiques
CLC-2 Chloride Channels
0
Chloride Channels
0
Clcn2 protein, mouse
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
662-674Subventions
Organisme : Università degli Studi di Trento
ID : Bando Progetti Strategici di Ateneo
Organisme : Fondazione Telethon
ID : TCP12013
Organisme : Muscular Dystrophy Association
ID : 479363
Organisme : Association Française contre les Myopathies
ID : 22221
Organisme : Provincia Autonoma di Trento (IT)
ID : Great project "MaDEleNA"
Organisme : Fondazione Cassa Di Risparmio Di Trento E Rovereto
ID : Bando Post-Doc
Organisme : Fondazione Cassa Di Risparmio Di Trento E Rovereto
ID : Bando Post-doc
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