ArticleThe Journal of biological chemistry2016
Transient Receptor Potential Canonical (TRPC)/Orai1-dependent Store-operated Ca2+ Channels: NEW TARGETS OF ALDOSTERONE IN CARDIOMYOCYTES.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- The mechanisms of exercise improving cardiovascular function by stimulating Piezo1 and TRP ion channels: a systemic review.Molecular and cellular biochemistry · 2025Pooled it
- The potential of TRPC channel-mediated autophagy in myocardial ischemia-reperfusion injury.Journal of cardiothoracic surgery · 2026Review
- Combination of Orai1 inhibitor CM5480 with specific therapy mitigates pulmonary hypertension and its cardiac dysfunction.JCI insight · 2025Article
- Mechanistic Insights and Therapeutic Potential of Wnt5a Signaling in Alveolar Epithelial Cell Development and Bronchopulmonary Dysplasia.Stem cell reviews and reports · 2025Review
- Early cardioprotective effects of SGLT2i on hypertensive cardiac remodeling via STIM1/Orai1-dependent calcium signaling: beyond blood pressure control.Journal of bioenergetics and biomembranes · 2025Article
- CaBiomedicines · 2025Review
- Inhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Store-Operated CaJournal of clinical medicine · 2023Review
- SKF96365 modulates activity of CatSper channels in human sperm.Molecular human reproduction · 2023Article
- The Molecular Heterogeneity of Store-Operated CaInternational journal of molecular sciences · 2023Review
- The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.Cells · 2022Review
- STIM1-Orai1 interaction mediated calcium influx activation contributes to cardiac contractility of insulin-resistant rats.BMC cardiovascular disorders · 2022Article
- Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- TRPC1 channels underlie stretch-modulated sarcoplasmic reticulum calcium leak in cardiomyocytes.Frontiers in physiology · 2022Article
- Aldosterone-Induced Sarco/Endoplasmic Reticulum CaFrontiers in physiology · 2022Article
- TRPC3, but not TRPC1, as a good therapeutic target for standalone or complementary treatment of DMD.Journal of translational medicine · 2021Article
- Role of Store-Operated CaBiomolecules · 2021Review
- GSK1702934A and M085 directly activate TRPC6 via a mechanism of stimulating the extracellular cavity formed by the pore helix and transmembrane helix S6.The Journal of biological chemistry · 2021Article
- The interplay between mitochondria and store-operated CaJournal of cellular and molecular medicine · 2021Review
- Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts.Cells · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Store-operated Ca(2+) entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca(2+) influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes. Molecular screening using qRT-PCR and Western blotting demonstrated that aldosterone treatment for 24 h specifically increased the mRNA and/or protein levels of Orai1, TRPC1, -C4, -C5, and stromal interaction molecule 1 through MR activation. These effects were correlated with a specific enhancement of SOCE activities sensitive to store-operated channel inhibitors (SKF-96365 and BTP2) and to a potent Orai1 blocker (S66) and were prevented by TRPC1, -C4, and Orai1 dominant negative mutants or TRPC5 siRNA. A mechanistic approach showed that up-regulation of serum- and glucocorticoid-regulated kinase 1 mRNA expression by aldosterone is involved in enhanced SOCE. Functionally, 24-h aldosterone-enhanced SOCE is associated with increased diastolic [Ca(2+)]i, which is blunted by store-operated channel inhibitors. Our study provides the first evidence that aldosterone promotes TRPC1-, -C4-, -C5-, and Orai1-mediated SOCE in cardiomyocytes through an MR and serum- and glucocorticoid-regulated kinase 1 pathway.
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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.