ArticleJournal of molecular and cellular cardiology2015
Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells: Kinetics of PKA activation in heart pacemaker cells.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Intracellular CaInternational journal of molecular sciences · 2026Article
- PKA restricts ERK signaling in learning and memory Kenyon cell neurons.Cellular signalling · 2025Article
- Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids.iScience · 2025Article
- Agonizing GABAFrontiers in pharmacology · 2025Article
- Cardiac optogenetics: shining light on signaling pathways.Pflugers Archiv : European journal of physiology · 2023Review
- Lipopolysaccharide-induced sepsis impairs M2R-GIRK signaling in the mouse sinoatrial node.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Synergy between Membrane Currents Prevents Severe Bradycardia in Mouse Sinoatrial Node Tissue.International journal of molecular sciences · 2023Article
- cAMP-PKA signaling modulates the automaticity of human iPSC-derived cardiomyocytes.The Journal of general physiology · 2023Article
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- Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond.International journal of molecular sciences · 2021Review
- CaFrontiers in physiology · 2021Article
- Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches.The Journal of physiology · 2020Review
- Beating Rate Variability of Isolated Mammal Sinoatrial Node Tissue: Insight Into Its Contribution to Heart Rate Variability.Frontiers in neuroscience · 2020Article
- Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans.Frontiers in physiology · 2020Review
- May the Force Not Be With You During Culture: Eliminating Mechano-Associated Feedback During Culture Preserves Cultured Atrial and Pacemaker Cell Functions.Frontiers in physiology · 2020Review
- Eliminating contraction during culture maintains global and local CaCell calcium · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PKA activity match the increase in AP firing rate in response to β-adrenergic receptor (β-AR) stimulation or phosphodiesterase (PDE) inhibition, that alters the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirus expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of β-AR stimulation (by Isoproterenol) the magnitude of the increases in PKA activity and the spontaneous AP firing rate were similar (0.4±0.1nM vs. 0.6±0.15nM, respectively). Moreover, the kinetics (t1/2) of the increases in PKA activity and spontaneous AP firing rate in response to β-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into a mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PKA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (β-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca(2+)-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate.
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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.