ArticleEuropean heart journal2015
A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling.
Article in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 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
- Transient receptor potential channels as key regulators of cell death in atherosclerosis.Frontiers in immunology · 2025Review
- Unlocking the potential of cardiac TRP channels using knockout mice models.Frontiers in physiology · 2025Article
- TRPC3 contributes to cyclophosphamide-induced cystitis progression by enhancing bladder fibrosis through activation of the TGF-β/smad pathway.Frontiers in pharmacology · 2025Article
- Familial Dilated Cardiomyopathy: A Novel MED9 Short Isoform Identification.International journal of molecular sciences · 2024Article
- SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.PloS one · 2024Article
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.Cells · 2022Review
- Interaction of background CaThe Journal of physiology · 2022Article
- Role of store-operated Ca2+ entry in cardiovascular disease.Cell communication and signaling : CCS · 2022Review
- Effects of Sarcolemmal Background CaFrontiers in physiology · 2022Article
- Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology.Frontiers in physiology · 2022Review
- Gestational diabetes triggers postpartum cardiac hypertrophy via activation of calcineurin/NFAT signaling.Scientific reports · 2021Article
- The interplay between mitochondria and store-operated CaJournal of cellular and molecular medicine · 2021Review
- Calcium and Heart Failure: How Did We Get Here and Where Are We Going?International journal of molecular sciences · 2021Review
- Transcriptome and proteome mapping in the sheep atria reveal molecular featurets of atrial fibrillation progression.Cardiovascular research · 2021Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Store-Operated Calcium Entry in the Cardiovascular System.Advances in experimental medicine and biology · 2021Review
- Trpc6 Promotes Doxorubicin-Induced Cardiomyopathy in Male Mice With Pleiotropic Differences Between Males and Females.Frontiers in cardiovascular medicine · 2021Article
- 1-MNA Ameliorates High Fat Diet-Induced Heart Injury by Upregulating Nrf2 Expression and Inhibiting NF-κBFrontiers in cardiovascular medicine · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
aimsPathological cardiac hypertrophy is a major predictor for the development of cardiac diseases. It is associated with chronic neurohumoral stimulation and with altered cardiac Ca(2+) signalling in cardiomyocytes. TRPC proteins form agonist-induced cation channels, but their functional role for Ca(2+) homeostasis in cardiomyocytes during fast cytosolic Ca(2+) cycling and neurohumoral stimulation leading to hypertrophy is unknown. METHODS AND
resultsIn a systematic analysis of multiple knockout mice using fluorescence imaging of electrically paced adult ventricular cardiomyocytes and Mn(2+)-quench microfluorimetry, we identified a background Ca(2+) entry (BGCE) pathway that critically depends on TRPC1/C4 proteins but not others such as TRPC3/C6. Reduction of BGCE in TRPC1/C4-deficient cardiomyocytes lowers diastolic and systolic Ca(2+) concentrations both, under basal conditions and under neurohumoral stimulation without affecting cardiac contractility measured in isolated hearts and in vivo. Neurohumoral-induced cardiac hypertrophy as well as the expression of foetal genes (ANP, BNP) and genes regulated by Ca(2+)-dependent signalling (RCAN1-4, myomaxin) was reduced in TRPC1/C4 knockout (DKO), but not in TRPC1- or TRPC4-single knockout mice. Pressure overload-induced hypertrophy and interstitial fibrosis were both ameliorated in TRPC1/C4-DKO mice, whereas they did not show alterations in other cardiovascular parameters contributing to systemic neurohumoral-induced hypertrophy such as renin secretion and blood pressure.
conclusionsThe constitutively active TRPC1/C4-dependent BGCE fine-tunes Ca(2+) cycling in beating adult cardiomyocytes. TRPC1/C4-gene inactivation protects against development of maladaptive cardiac remodelling without altering cardiac or extracardiac functions contributing to this pathogenesis.
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