en
Scientific article
Open access
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
Commercial URLhttps://rdcu.be/bb8qf
ISSN of the journal0022-3751
385views
176downloads

Technical informations

Creation11/29/2018 2:45:00 PM
First validation11/29/2018 2:45:00 PM
Update time03/15/2023 4:05:50 PM
Status update03/15/2023 4:05:49 PM
Last indexation05/03/2024 8:19:51 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack