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• W2023378795 endingPage "243" @default.
• W2023378795 startingPage "235" @default.
• W2023378795 abstract "Deviations from physiological pH (∼pH 7.2) as well as altered Ca(2+) signaling play important roles in immune disease and cancer. One of the most ubiquitous pathways for cellular Ca(2+) influx is the store-operated Ca(2+) entry (SOCE) or Ca(2+) release-activated Ca(2+) current (ICRAC), which is activated upon depletion of intracellular Ca(2+) stores. We here show that extracellular and intracellular changes in pH regulate both endogenous ICRAC in Jurkat T lymphocytes and RBL2H3 cells, and heterologous ICRAC in HEK293 cells expressing the molecular components STIM1/2 and Orai1/2/3 (CRACM1/2/3). We find that external acidification suppresses, and alkalization facilitates IP3-induced ICRAC. In the absence of IP3, external alkalization did not elicit endogenous ICRAC but was able to activate heterologous ICRAC in HEK293 cells expressing Orai1/2/3 and STIM1 or STIM2. Similarly, internal acidification reduced IP3-induced activation of endogenous and heterologous ICRAC, while alkalization accelerated its activation kinetics without affecting overall current amplitudes. Mutation of two aspartate residues to uncharged alanine amino acids (D110/112A) in the first extracellular loop of Orai1 significantly attenuated both the inhibition of ICRAC by external acidic pH as well as its facilitation by alkaline conditions. We conclude that intra- and extracellular pH differentially regulates ICRAC. While intracellular pH might affect aggregation and/or binding of STIM to Orai, external pH seems to modulate ICRAC through its channel pore, which in Orai1 is partially mediated by residues D110 and D112." @default.
• W2023378795 created "2016-06-24" @default.
• W2023378795 creator A5035115736 @default.
• W2023378795 creator A5058943509 @default.
• W2023378795 creator A5064410327 @default.
• W2023378795 creator A5081265038 @default.
• W2023378795 date "2014-09-01" @default.
• W2023378795 modified "2023-10-18" @default.
• W2023378795 title "Regulation of endogenous and heterologous Ca2+ release-activated Ca2+ currents by pH" @default.
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• W2023378795 doi "https://doi.org/10.1016/j.ceca.2014.07.011" @default.
• W2023378795 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4162834" @default.
• W2023378795 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25168908" @default.
• W2023378795 hasPublicationYear "2014" @default.
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