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Properties of Orai1 mediated store‐operated current depend on the expression levels of STIM1 and Orai1 proteins
Author(s) -
Scrimgeour N.,
Litjens T.,
Ma L.,
Barritt G. J.,
Rychkov G. Y.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.170662
Subject(s) - orai1 , stim1 , chemistry , endoplasmic reticulum , biophysics , microbiology and biotechnology , divalent , biochemistry , biology , organic chemistry
Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca 2+ release activated Ca 2+ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca 2+ sensor required for activation of CRAC current ( I CRAC ) by store depletion. It is not known, however, if the role of STIM1 is limited exclusively to Ca 2+ sensing, or whether interaction between Orai1 and STIM1, either direct or indirect, also defines the properties of I CRAC . In this study we investigated how the relative expression levels of ectopic Orai1 and STIM1 affect the properties of I CRAC . The results show that cells expressing low Orai1 : STIM1 ratios produce I CRAC with strong fast Ca 2+ ‐dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce I CRAC with strong activation at negative potentials. Moreover, the expression ratio of Orai1 and STIM1 affects Ca 2+ , Ba 2+ and Sr 2+ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca 2+ channels formed by Orai1 depend on its interaction with STIM1, and that the stoichiometry of this interaction may vary depending on the relative expression levels of these proteins.