ArticleCirculation research2012
Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- 17β-Estradiol inhibits phosphorylation of stromal interaction molecule 1 (STIM1) protein: implication for store-operated calcium entry and chronic lung diseases.The Journal of biological chemistry · 2013Trial
- The machinery of healthy vasoconstriction: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- The Calcium Signalling Profile of the Inner Blood-Retinal Barrier in Diabetic Retinopathy.Cells · 2025Review
- CaBiomedicines · 2025Review
- The Molecular Heterogeneity of Store-Operated CaInternational journal of molecular sciences · 2023Review
- Heteromeric TRP Channels in Lung Inflammation.Cells · 2021Review
- Impact of Na+ permeation on collective migration of pulmonary arterial endothelial cells.PloS one · 2021Article
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- S100A6 is a positive regulator of PPP5C-FKBP51-dependent regulation of endothelial calcium signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Regulation of Vessel Permeability by TRP Channels.Frontiers in physiology · 2020Review
- Endothelial CaInternational journal of molecular sciences · 2019Review
- Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.Comprehensive Physiology · 2019Review
- Pharmacological characterization of the calcium influx pathways involved in nitric oxide production by endothelial cells.Einstein (Sao Paulo, Brazil) · 2019Article
- αAmerican journal of physiology. Cell physiology · 2019Article
- Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular CaFrontiers in physiology · 2019Review
- The Role of Endothelial CaInternational journal of molecular sciences · 2018Review
- Reduced membrane cholesterol after chronic hypoxia limits Orai1-mediated pulmonary endothelial CaAmerican journal of physiology. Heart and circulatory physiology · 2018Article
- Endothelial CaInternational journal of molecular sciences · 2018Review
- Calcium permeability of transient receptor potential canonical (TRPC) 4 channels measured by TRPC4-GCaMP6s.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Endothelial hyperpermeability in severe pulmonary arterial hypertension: role of store-operated calcium entry.American journal of physiology. Lung cellular and molecular physiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleCanonical transient receptor potential 4 (TRPC4) contributes to the molecular composition of a channel encoding for a calcium selective store-operated current, I(SOC), whereas Orai1 critically comprises a channel encoding for the highly selective calcium release activated calcium current, I(CRAC). However, Orai1 may interact with TRPC proteins and influence their activation and permeation characteristics. Endothelium expresses both TRPC4 and Orai1, and it remains unclear as to whether Orai1 interacts with TRPC4 and contributes to calcium permeation through the TPRC4 channel.
objectiveWe tested the hypothesis that Orai1 interacts with TRPC4 and contributes to the channel's selective calcium permeation important for endothelial barrier function. METHODS AND
resultsA novel method to purify the endogenous TRPC4 channel and probe for functional interactions was developed, using TRPC4 binding to protein 4.1 as bait. Isolated channel complexes were conjugated to anti-TRPC protein antibodies labeled with cy3-cy5 pairs. Förster Resonance Energy Transfer among labeled subunits revealed the endogenous protein alignment. One TRPC1 and at least 2 TRPC4 subunits constituted the endogenous channel (TRPC1/4). Orai1 interacted with TRPC4. Conditional Orai1 knockdown reduced the probability for TRPC1/4 channel activation and converted it from a calcium-selective to a nonselective channel, an effect that was rescued on Orai1 reexpression. Loss of Orai1 improved endothelial cell barrier function.
conclusionOrai1 interacts with TRPC4 in the endogenous channel complex, where it controls TRPC1/4 activation and channel permeation characteristics, including calcium selectivity, important for control of endothelial cell barrier function.
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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.