ArticleCardiovascular research2016
Intracellular tortuosity underlies slow cAMP diffusion in adult ventricular myocytes.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Statistical analysis of fluorescence intensity transients with Bayesian methods.Science advances · 2025Article
- cAMP signaling: a remarkably regional affair.Trends in biochemical sciences · 2024Review
- Longitudinal diffusion barriers imposed by myofilaments and mitochondria in murine cardiac myocytes.The Journal of general physiology · 2023Article
- Pore-like diffusion barriers in murine cardiac myocytes.bioRxiv : the preprint server for biology · 2023Article
- Ontogeny of cardiomyocytes: ultrastructure optimization to meet the demand for tight communication in excitation-contraction coupling and energy transfer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022Article
- The organic cation transporter 2 regulates dopamine D1 receptor signaling at the Golgi apparatus.eLife · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Compartmentalized cAMP signaling in cardiac ventricular myocytes.Cellular signalling · 2022Review
- Mechanisms of cAMP compartmentation in cardiac myocytes: experimental and computational approaches to understanding.The Journal of physiology · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Nitric oxide modulates cardiomyocyte pH control through a biphasic effect on sodium/hydrogen exchanger-1.Cardiovascular research · 2020Article
- Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.Cell · 2020Article
- Article
- Dual Activation of cAMP Production Through Photostimulation or Chemical Stimulation.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Nanometric targeting of type 9 adenylyl cyclase in heart.Biochemical Society transactions · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
aims3',5'-Cyclic adenosine monophosphate (cAMP) signals in the heart are often confined to concentration microdomains shaped by cAMP diffusion and enzymatic degradation. While the importance of phosphodiesterases (degradative enzymes) in sculpting cAMP microdomains is well established in cardiomyocytes, less is known about cAMP diffusivity (DcAMP) and factors affecting it. Many earlier studies have reported fast diffusivity, which argues against sharply defined microdomains. METHODS AND
results[cAMP] dynamics in the cytoplasm of adult rat ventricular myocytes were imaged using a fourth generation genetically encoded FRET-based sensor. The [cAMP]-response to the addition and removal of isoproterenol (β-adrenoceptor agonist) quantified the rates of cAMP synthesis and degradation. To obtain a read out of DcAMP, a stable [cAMP] gradient was generated using a microfluidic device which delivered agonist to one half of the myocyte only. After accounting for phosphodiesterase activity, DcAMP was calculated to be 32 µm(2)/s; an order of magnitude lower than in water. Diffusivity was independent of the amount of cAMP produced. Saturating cAMP-binding sites with the analogue 6-Bnz-cAMP did not accelerate DcAMP, arguing against a role of buffering in restricting cAMP mobility. cAMP diffused at a comparable rate to chemically unrelated but similar sized molecules, arguing for a common physical cause of restricted diffusivity. Lower mitochondrial density and order in neonatal cardiac myocytes allowed for faster diffusion, demonstrating the importance of mitochondria as physical barriers to cAMP mobility.
conclusionIn adult cardiac myocytes, tortuosity due to physical barriers, notably mitochondria, restricts cAMP diffusion to levels that are more compatible with microdomain signalling.
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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.