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Article scientifique
Accès libre
Anglais

ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain

Date de publication2018
Résumé

Gain-of-function mutations in the highly selective Ca2+ channel ORAI1 cause tubular aggregate myopathy (TAM) characterized by muscular pain, weakness and cramping. TAM-associated mutations in ORAI1 first and third transmembrane domain facilitate channel opening by STIM1, causing constitutive Ca2+ influx and increasing the currents evoked by Ca2+ store depletion. Mutation V107M additionally decreases the channel selectivity for Ca2+ ions and its inhibition by acidic pH, while mutation T184M does not alter the channel sensitivity to pH or to reactive oxygen species. The ORAI blocker GSK-7975A prevents the constitutive activity of TAM-associated channels and might be used in therapy for patients suffering from TAM.

Financement
  • Swiss National Science Foundation - 31003A‐149566
  • Swiss National Science Foundation - CRSII3‐16078
Citation (format ISO)
BULLA, Monica et al. ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain. In: The Journal of Physiology, 2018. doi: 10.1113/JP277079
Fichiers principaux (1)
Article (Published version)
Identifiants
URL commercialhttps://rdcu.be/bb8qf
ISSN du journal0022-3751
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Informations techniques

Création29/11/2018 14:45:00
Première validation29/11/2018 14:45:00
Heure de mise à jour15/03/2023 16:05:50
Changement de statut15/03/2023 16:05:49
Dernière indexation12/02/2024 11:39:39
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