Regulation of Orai1/STIM1 mediated ICRAC by intracellular pH

D Gavriliouk, N Scrimgeour, S Grigoryev, L Ma, F Zhou, G Barritt, G Rychkov

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7 Citations (Scopus)


Ca 2+ release activated Ca 2+ (CRAC) channels composed of two cellular proteins, Ca 2+ -sensing stromal interaction molecule 1 (STIM1) and pore-forming Orai1, are the main mediators of the Ca 2+ entry pathway activated in response to depletion of intracellular Ca 2+ stores. Previously it has been shown that the amplitude of CRAC current (I CRAC ) strongly depends on extracellular and intracellular pH. Here we investigate the intracellular pH (pH i ) dependence of I CRAC mediated by Orai1 and STIM1ectopically expressed in HEK293 cells. The results indicate that pH i affects not only the amplitude of the current, but also Ca 2+ dependent gating of CRAC channels. Intracellular acidification changes the kinetics of I CRAC , introducing prominent re-activation component in the currents recorded in response to voltage steps to strongly negative potentials. I CRAC with similar kinetics can be observed at normal pH i if the expression levels of Orai1 are increased, relative to the expression levels of STIM1. Mutations in the STIM1 inactivation domain significantly diminish the dependence of I CRAC kinetics on pH i , but have no effect on pH i dependence of I CRAC amplitude, implying that more than one mechanism is involved in CRAC channel regulation by intracellular pH.

Original languageEnglish
Article number9829
Number of pages12
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2017


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