Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins

Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca²⁺ release activated Ca²⁺ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca²⁺ 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 Ca²⁺ 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 Ca²⁺-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 Ca²⁺, Ba²⁺ and Sr²⁺ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca²⁺ 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.