ArticleProceedings of the National Academy of Sciences of the United States of America2013
Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- 14-3-3 promotes sarcolemmal expression of cardiac CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- β-adrenergic regulation of CaBiophysics reports · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- αeLife · 2023Article
- Phosphorylation, compartmentalization, and cardiac function.IUBMB life · 2023Article
- Impairment of β-adrenergic regulation and exacerbation of pressure-induced heart failure in mice with mutations in phosphoregulatory sites in the cardiac CaFrontiers in physiology · 2023Article
- Spatiotemporal Control of Vascular CaCirculation research · 2022Article
- Convergent regulation of CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sites and Regulation of L-Type CaCellular and molecular neurobiology · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- Use of Proximity Labeling in Cardiovascular Research.JACC. Basic to translational science · 2021Review
- Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension.Oxidative medicine and cellular longevity · 2021Article
- The quest to identify the mechanism underlying adrenergic regulation of cardiac CaChannels (Austin, Tex.) · 2020Review
- Protein kinase CK2 and ion channels (Review).Biomedical reports · 2020Review
- Protein Kinase CK2 Controls CaInternational journal of molecular sciences · 2020Article
- Suspect that modulates the heartbeat is ensnared.Nature · 2020Article
- Voltage-gated calcium channels: their discovery, function and importance as drug targets.Brain and neuroscience advances · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
L-type Ca(2+) currents conducted by CaV1.2 channels initiate excitation-contraction coupling in the heart. Their activity is increased by β-adrenergic/cAMP signaling via phosphorylation by PKA in the fight-or-flight response, but the sites of regulation are unknown. We describe the functional role of phosphorylation of Ser1700 and Thr1704-sites of phosphorylation by PKA and casein kinase II at the interface between the proximal and distal C-terminal regulatory domains. Mutation of both residues to Ala in STAA mice reduced basal L-type Ca(2+) currents, due to a small decrease in expression and a substantial decrease in functional activity. The increase in L-type Ca(2+) current caused by isoproterenol was markedly reduced at physiological levels of stimulation (3-10 nM). Maximal increases in calcium current at nearly saturating concentrations of isoproterenol (100 nM) were also significantly reduced, but the mutation effects were smaller, suggesting that alternative regulatory mechanisms are engaged at maximal levels of stimulation. The β-adrenergic increase in cell contraction was also diminished. STAA ventricular myocytes exhibited arrhythmic contractions in response to isoproterenol, and up to 20% of STAA cells failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. We conclude that phosphorylation of Ser1700 and Thr1704 is essential for regulation of basal activity of CaV1.2 channels and for up-regulation by β-adrenergic signaling at physiological levels of stimulation. Disruption of phosphorylation at those sites leads to impaired cardiac function in vivo, as indicated by reduced exercise capacity and cardiac hypertrophy.
Indexed as
Identifiers
What OpenQuestion holds
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.