ArticleThe Journal of clinical investigation2009
alpha1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 87 citations in OpenAlex.
- The Dysfunction of CaInternational journal of molecular sciences · 2023Review
- Connexin 43 hyper-phosphorylation at serine 282 triggers apoptosis in rat cardiomyocytes via activation of mitochondrial apoptotic pathway.Acta pharmacologica Sinica · 2022Article
- The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaBiomedicines · 2022Article
- The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy.Scientific reports · 2021Article
- A low voltage activated CaChannels (Austin, Tex.) · 2020Article
- Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins.Pflugers Archiv : European journal of physiology · 2020Review
- T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions.Scientific reports · 2020Article
- Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart.Scientific reports · 2018Article
- Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy.Chinese journal of integrative medicine · 2018Article
- Increasing T-type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates.The Journal of physiology · 2018Article
- T-type CaChannels (Austin, Tex.) · 2017Review
- Cardiac-directed expression of a catalytically inactive adenylyl cyclase 6 protects the heart from sustained β-adrenergic stimulation.PloS one · 2017Article
- Tetrodotoxin-sensitive Ca2+ Currents, but No T-type Currents in Normal, Hypertrophied, and Failing Mouse Cardiomyocytes.Journal of cardiovascular pharmacology · 2016Article
- Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy.Molecular medicine (Cambridge, Mass.) · 2016Article
- Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes.Cell research · 2016Article
- Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes.The Journal of biological chemistry · 2015Article
- The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart.Cell reports · 2015Article
- Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.Journal of molecular and cellular cardiology · 2015Article
- Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling.Molecular and cellular biology · 2015Article
- Eps15 Homology Domain-containing Protein 3 Regulates Cardiac T-type Ca2+ Channel Targeting and Function in the Atria.The Journal of biological chemistry · 2015Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
In noncontractile cells, increases in intracellular Ca2+ concentration serve as a second messenger to signal proliferation, differentiation, metabolism, motility, and cell death. Many of these Ca2+-dependent regulatory processes operate in cardiomyocytes, although it remains unclear how Ca2+ serves as a second messenger given the high Ca2+ concentrations that control contraction. T-type Ca2+ channels are reexpressed in adult ventricular myocytes during pathologic hypertrophy, although their physiologic function remains unknown. Here we generated cardiac-specific transgenic mice with inducible expression of alpha1G, which generates Cav3.1 current, to investigate whether this type of Ca2+ influx mechanism regulates the cardiac hypertrophic response. Unexpectedly, alpha1G transgenic mice showed no cardiac pathology despite large increases in Ca2+ influx, and they were even partially resistant to pressure overload-, isoproterenol-, and exercise-induced cardiac hypertrophy. Conversely, alpha1G-/- mice displayed enhanced hypertrophic responses following pressure overload or isoproterenol infusion. Enhanced hypertrophy and disease in alpha1G-/- mice was rescued with the alpha1G transgene, demonstrating a myocyte-autonomous requirement of alpha1G for protection. Mechanistically, alpha1G interacted with NOS3, which augmented cGMP-dependent protein kinase type I activity in alpha1G transgenic hearts after pressure overload. Further, the anti-hypertrophic effect of alpha1G overexpression was abrogated by a NOS3 inhibitor and by crossing the mice onto the Nos3-/- background. Thus, cardiac alpha1G reexpression and its associated pool of T-type Ca2+ antagonize cardiac hypertrophy through a NOS3-dependent signaling mechanism.
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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.