Clenbuterol-sensitive delayed outward potassium currents in a cell model of spinal and bulbar muscular atrophy.
Clenbuterol
Ion channels
Kv2 potassium channels
Outward ionic currents
PolyQ AR MN-1 cells
Spinal and bulbar muscular atrophy (SBMA)
Journal
Pflugers Archiv : European journal of physiology
ISSN: 1432-2013
Titre abrégé: Pflugers Arch
Pays: Germany
ID NLM: 0154720
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
26
01
2021
accepted:
23
03
2021
revised:
09
03
2021
pubmed:
23
5
2021
medline:
4
2
2022
entrez:
22
5
2021
Statut:
ppublish
Résumé
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. SBMA is characterized by selective dysfunction and degeneration of motor neurons in the brainstem and spinal cord through still unclear mechanisms in which ion channel modulation might play a central role as for other neurodegenerative diseases. The beta2-adrenergic agonist clenbuterol was observed to ameliorate the SBMA phenotype in mice and patient-derived myotubes. However, the underlying molecular mechanism has yet to be clarified. Here, we unveil that ionic current alterations induced by the expression of polyQ-expanded AR in motor neuron-derived MN-1 cells are attenuated by the administration of clenbuterol. Our combined electrophysiological and pharmacological approach allowed us to reveal that clenbuterol modifies delayed outward potassium currents. Overall, we demonstrated that the protection provided by clenbuterol restores the normal function through the modulation of K
Identifiants
pubmed: 34021780
doi: 10.1007/s00424-021-02559-6
pii: 10.1007/s00424-021-02559-6
doi:
Substances chimiques
Arthropod Proteins
0
Delayed Rectifier Potassium Channels
0
GxTX-1E, Plesiophrictus guangxiensis
0
Spider Venoms
0
Clenbuterol
XTZ6AXU7KN
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1213-1227Subventions
Organisme : NINDS NIH HHS
ID : R21 NS111768
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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