ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Mechanisms that match ATP supply to demand in cardiac pacemaker cells during high ATP demand.
Article in American journal of physiology. Heart and circulatory physiology, 2013. 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, 39 citations in OpenAlex.
- Intracellular CaInternational journal of molecular sciences · 2026Article
- cAMP-Activated EPAC Signaling Is an Integral Component of Cardiac Pacemaker Cell Automaticity.Circulation. Arrhythmia and electrophysiology · 2026Article
- Beat-locked ATP microdomains in the sinoatrial node map a Ca2+-timed energetic hierarchy and regional pacemaker roles.The Journal of general physiology · 2026Article
- Demonstration of beat-to-beat, on-demand ATP synthesis in ventricular myocytes reveals sex-specific mitochondrial and cytosolic dynamics.The Journal of physiology · 2026Article
- Heart Rhythm Harmony Becomes Discordant as We Age.Heart, lung & circulation · 2025Review
- Proteomics Reveals Divergent Cardiac Inflammatory and Metabolic Responses After Inhalation of Ambient Particulate Matter With or Without Ozone.Cardiovascular toxicology · 2024Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Article
- Changes in the Concentration of Purine and Pyridine as a Response to Single Whole-Body Cryostimulation.Frontiers in physiology · 2021Article
- 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
- Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics.Journal of the American Heart Association · 2018Article
- Unique CaInternational journal of molecular sciences · 2018Review
- Aberrant Mitochondrial Fission Is Maladaptive in Desmin Mutation-Induced Cardiac Proteotoxicity.Journal of the American Heart Association · 2018Article
- Aging, inflammation and the environment.Experimental gerontology · 2018Review
- Regulation of ATP utilization during metastatic cell migration by collagen architecture.Molecular biology of the cell · 2018Article
- A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells.Frontiers in physiology · 2017Article
- Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.Journal of molecular and cellular cardiology · 2016Article
- Article
- Electrochemical Na+ and Ca2+ gradients drive coupled-clock regulation of automaticity of isolated rabbit sinoatrial nodal pacemaker cells.American journal of physiology. Heart and circulatory physiology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The spontaneous action potential (AP) firing rate of sinoatrial node cells (SANCs) involves high-throughput signaling via Ca(2+)-calmodulin activated adenylyl cyclases (AC), cAMP-mediated protein kinase A (PKA), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of SR Ca(2+) cycling and surface membrane ion channel proteins. When the throughput of this signaling increases, e.g., in response to β-adrenergic receptor activation, the resultant increase in spontaneous AP firing rate increases the demand for ATP. We hypothesized that an increase of ATP production to match the increased ATP demand is achieved via a direct effect of increased mitochondrial Ca(2+) (Ca(2+)m) and an indirect effect via enhanced Ca(2+)-cAMP/PKA-CaMKII signaling to mitochondria. To increase ATP demand, single isolated rabbit SANCs were superfused by physiological saline at 35 ± 0.5°C with isoproterenol, or by phosphodiesterase or protein phosphatase inhibition. We measured cytosolic and mitochondrial Ca(2+) and flavoprotein fluorescence in single SANC, and we measured cAMP, ATP, and O₂ consumption in SANC suspensions. Although the increase in spontaneous AP firing rate was accompanied by an increase in O₂ consumption, the ATP level and flavoprotein fluorescence remained constant, indicating that ATP production had increased. Both Ca(2+)m and cAMP increased concurrently with the increase in AP firing rate. When Ca(2+)m was reduced by Ru360, the increase in spontaneous AP firing rate in response to isoproterenol was reduced by 25%. Thus, both an increase in Ca(2+)m and an increase in Ca(2+) activated cAMP-PKA-CaMKII signaling regulate the increase in ATP supply to meet ATP demand above the basal level.
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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.