ArticleCell calcium2014
Regulation of endogenous and heterologous Ca²⁺ release-activated Ca²⁺ currents by pH.
Article in Cell calcium, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Functional model for amelogenesis: polarization and pH sensitivity of calcium uptake in ameloblast-derived HAT-7 cells.Calcified tissue international · 2026Article
- A Hidden Checkpoint: Bidirectional pH Remodeling of the Immunological Synapse in Cancer, Methods, and Therapeutic Opportunities.Journal of immunology research · 2026Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes.Life (Basel, Switzerland) · 2024Article
- Implications of pH and Ionic Environment in Chronic Diabetic Wounds: An Overlooked Perspective.Clinical, cosmetic and investigational dermatology · 2024Review
- Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- CaInternational journal of molecular sciences · 2022Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Orai2 Modulates Store-Operated CaCancers · 2021Article
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Calcium Channel Protein ORAI1 Mediates TGF-β Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells.Frontiers in oncology · 2021Article
- Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels.Cell calcium · 2020Article
- Triclosan disrupts immune cell function by depressing CaToxicology and applied pharmacology · 2020Article
- T-cells produce acidic niches in lymph nodes to suppress their own effector functions.Nature communications · 2020Article
- Single-nucleotide polymorphisms in Orai1 associated with atopic dermatitis inhibit protein turnover, decrease calcium entry and disrupt calcium-dependent gene expression.Human molecular genetics · 2020Article
- Molecular understanding of calcium permeation through the open Orai channel.PLoS biology · 2019Article
- ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain.The Journal of physiology · 2019Article
- High pH-Sensitive Store-Operated CaFrontiers in physiology · 2018Article
- Regulation of Orai1/STIM1 mediated IScientific reports · 2017Article
- CRAC channel gating and its modulation by STIM1 and 2-aminoethoxydiphenyl borate.The Journal of physiology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.