Scientific article
OA Policy
English

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

Publication date2018
Abstract

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.

Funding
  • Swiss National Science Foundation - 31003A‐149566
  • Swiss National Science Foundation - CRSII3‐16078
Citation (ISO format)
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
Main files (1)
Article (Published version)
Identifiers
Additional URL for this publicationhttps://rdcu.be/bb8qf
Journal ISSN0022-3751
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225downloads

Technical informations

Creation29/11/2018 14:45:00
First validation29/11/2018 14:45:00
Update time15/03/2023 16:05:50
Status update15/03/2023 16:05:49
Last indexation31/10/2024 13:08:11
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