ArticleCardiovascular research2009
Transgenic simulation of human heart failure-like L-type Ca2+-channels: implications for fibrosis and heart rate in mice.
Article in Cardiovascular research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Opposite effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
- Pro-Arrhythmic Effects of Discontinuous Conduction at the Purkinje Fiber-Ventricle Junction Arising From Heart Failure-Induced Ionic Remodeling - Insights From Computational Modelling.Frontiers in physiology · 2022Article
- Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation.Cardiovascular therapeutics · 2021Article
- Enhanced Depolarization Drive in Failing Rabbit Ventricular Myocytes: Calcium-Dependent and β-Adrenergic Effects on Late Sodium, L-Type Calcium, and Sodium-Calcium Exchange Currents.Circulation. Arrhythmia and electrophysiology · 2019Article
- Cardiac CaV1.2 channels require β subunits for β-adrenergic-mediated modulation but not trafficking.The Journal of clinical investigation · 2019Article
- Exclusion of alternative exon 33 of CaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling.European heart journal · 2015Article
- Robust Generation of Cardiomyocytes from Human iPS Cells Requires Precise Modulation of BMP and WNT Signaling.Stem cell reviews and reports · 2015Article
- Whole-exome sequencing in familial atrial fibrillation.European heart journal · 2014Article
- Age- and gender-related changes in ventricular performance in wild-type FVB/N mice as evaluated by conventional and vector velocity echocardiography imaging: a retrospective study.Ultrasound in medicine & biology · 2013Article
- β-adrenergic regulation of the L-type Ca2+ channel does not require phosphorylation of α1C Ser1700.Circulation research · 2013Article
- Effect of MANT-nucleotides on L-type calcium currents in murine cardiomyocytes.Naunyn-Schmiedeberg's archives of pharmacology · 2011Article
- Caveolin-3 regulates protein kinase A modulation of the Ca(V)3.2 (alpha1H) T-type Ca2+ channels.The Journal of biological chemistry · 2011Article
- Gαi2- and Gαi3-specific regulation of voltage-dependent L-type calcium channels in cardiomyocytes.PloS one · 2011Article
- {Alpha}2B-adrenoceptor deficiency leads to postnatal respiratory failure in mice.The Journal of biological chemistry · 2010Article
- {beta}1-Adrenergic receptor activation induces mouse cardiac myocyte death through both L-type calcium channel-dependent and -independent pathways.American journal of physiology. Heart and circulatory physiology · 2010Article
- Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.American journal of physiology. Heart and circulatory physiology · 2010Article
- Cardiac phenotype induced by a dysfunctional α 1C transgene: a general problem for the transgenic approach.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsCardiac L-type Ca(2+)-currents show distinct alterations in chronic heart failure, including increased single-channel activity and blunted adrenergic stimulation, but minor changes of whole-cell currents. Expression of L-type Ca(2+)-channel beta(2)-subunits is enhanced in human failing hearts. In order to determine whether prolonged alteration of Ca(2+)-channel gating by beta(2)-subunits contributes to heart failure pathogenesis, we generated and characterized transgenic mice with cardiac overexpression of a beta(2a)-subunit or the pore Ca(v)1.2 or both, respectively. METHODS AND
resultsFour weeks induction of cardiac-specific overexpression of rat beta(2a)-subunits shifted steady-state activation and inactivation of whole-cell currents towards more negative potentials, leading to increased Ca(2+)-current density at more negative test potentials. Activity of single Ca(2+)-channels was increased in myocytes isolated from beta(2a)-transgenic mice. Ca(2+)-current stimulation by 8-Br-cAMP and okadaic acid was blunted in beta(2a)-transgenic myocytes. In vivo investigation revealed hypotension and bradycardia upon Ca(v)1.2-transgene expression but not in mice only overexpressing beta(2a). Double-transgenics showed cardiac arrhythmia. Interstitial fibrosis was aggravated by the beta(2a)-transgene compared with Ca(v)1.2-transgene expression alone. Overt cardiac hypertrophy was not observed in any model.
conclusionCardiac overexpression of a Ca(2+)-channel beta(2a)-subunit alone is sufficient to induce Ca(2+)-channel properties characteristic of chronic human heart failure. beta(2a)-overexpression by itself did not induce cardiac hypertrophy or contractile dysfunction, but aggravated the development of arrhythmia and fibrosis in Ca(v)1.2-transgenic mice.
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