ArticleProceedings of the National Academy of Sciences of the United States of America2009
Beta-adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
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- Early Stage Morphogenesis of Transverse Tubules in Rat Cardiomyocytes: The Role of pBIN1.Circulation research · 2025Article
- β-adrenergic regulation of CaBiophysics reports · 2024Article
- Thirty years of CaBiophysics reports · 2024Article
- Dopamine, norepinephrine, and vasopressin accelerate particle transport velocity in murine tracheal epithelium via substance-specific receptor pathways: dependency on intra- and extracellular CaFrontiers in pharmacology · 2024Article
- Disorder in Ca2+ release unit locations confers robustness but cuts flexibility of heart pacemaking.The Journal of general physiology · 2022Article
- Mitochondrial Quality Control in the Heart: The Balance between Physiological and Pathological Stress.Biomedicines · 2022Review
- Calcium cycling as a mediator of thermogenic metabolism in adipose tissue.Molecular pharmacology · 2022Article
- Review
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Local hyperactivation of L-type CaScientific reports · 2021Article
- Acute Detubulation of Ventricular Myocytes Amplifies the Inhibitory Effect of Cholinergic Agonist on Intracellular CaFrontiers in physiology · 2021Article
- CaFrontiers in physiology · 2021Article
- Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Central role of IPCell death & disease · 2019Article
- βCirculation research · 2019Article
- Regulation of CaCell calcium · 2019Article
- IOCBIO Sparks detection and analysis software.PeerJ · 2019Article
- Unique CaInternational journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
As the most prototypical G protein-coupled receptor, beta-adrenergic receptor (betaAR) regulates the pace and strength of heart beating by enhancing and synchronizing L-type channel (LCC) Ca(2+) influx, which in turn elicits greater sarcoplasmic reticulum (SR) Ca(2+) release flux via ryanodine receptors (RyRs). However, whether and how betaAR-protein kinase A (PKA) signaling directly modulates RyR function remains elusive and highly controversial. By using unique single-channel Ca(2+) imaging technology, we measured the response of a single RyR Ca(2+) release unit, in the form of a Ca(2+) spark, to its native trigger, the Ca(2+) sparklet from a single LCC. We found that acute application of the selective betaAR agonist isoproterenol (1 microM, < or = 20 min) increased triggered spark amplitude in an LCC unitary current-independent manner. The increased ratio of Ca(2+) release flux underlying a Ca(2+) spark to SR Ca(2+) content indicated that betaAR stimulation helps to recruit additional RyRs in synchrony. Quantification of sparklet-spark kinetics showed that betaAR stimulation synchronized the stochastic latency and increased the fidelity (i.e., chance of hit) of LCC-RyR intermolecular signaling. The RyR modulation was independent of the increased SR Ca(2+) content. The PKA antagonists Rp-8-CPT-cAMP (100 microM) and H89 (10 microM) both eliminated these effects, indicating that betaAR acutely modulates RyR activation via the PKA pathway. These results demonstrate unequivocally that RyR activation by a single LCC is accelerated and synchronized during betaAR stimulation. This molecular mechanism of sympathetic regulation will permit more fundamental studies of altered betaAR effects in cardiovascular diseases.
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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.