ArticleNature cardiovascular research2022
Rad regulation of Ca
Article in Nature cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- A Seven Amino Acid Long Region in the Cardiac CaCells · 2026Article
- 14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses.The Journal of physiology · 2026Review
- CaThe Journal of physiology · 2026Article
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Loss of phospholamban phosphorylation blunts CaJournal of molecular and cellular cardiology · 2026Article
- Context-Dependent Control: PKA Regulation of Vascular CaArteriosclerosis, thrombosis, and vascular biology · 2026Article
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- International Utah cardiac recovery symposium (U-CARS) 2025:translational and basic science proceedings.Heart failure reviews · 2026Review
- L-Type CaCirculation research · 2026Article
- Amyloid β alters vascular CaThe Journal of physiology · 2025Article
- Nanoscale architecture and dynamics of CaJournal of molecular and cellular cardiology plus · 2025Article
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- The genetic architecture of cervical length is shared with spontaneous preterm birth risk.Communications medicine · 2025Article
- Casein Kinase 2 Regulates the Intrinsic Activity of L-Type Calcium Currents in Cardiomyocytes.International journal of molecular sciences · 2025Article
- Probing the CabioRxiv : the preprint server for biology · 2025Article
- 14-3-3 promotes sarcolemmal expression of cardiac CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interleukin 11 therapy causes acute left ventricular dysfunction.Cardiovascular research · 2024Article
- Role of the CaChannels (Austin, Tex.) · 2024Article
- Rad-mediated inhibition of CaThe Journal of physiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished exercise capacity. Conversely, expression of mutant calcium-channel β-subunits that cannot bind 4SA-Rad is sufficient to enhance basal calcium influx and contractility to adrenergically augmented levels of wild-type mice, rescuing the failing heart phenotype of 4SA-Rad mice. Hence, disruption of interactions between Rad and calcium channels constitutes the foundation toward next-generation therapeutics specifically enhancing cardiac contractility.
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.