ArticleThe Journal of physiology2003
Role of cyclic nucleotide phosphodiesterase isoforms in cAMP compartmentation following beta2-adrenergic stimulation of ICa,L in frog ventricular myocytes.
Article in The Journal of physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 65 citations in OpenAlex.
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Article
- Phosphodiesterases 3 and 4 Differentially Regulate the Funny Current, IJournal of cardiovascular development and disease · 2017Article
- Differences in the control of basal L-type Ca(2+) current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes.The journal of physiological sciences : JPS · 2016Article
- MRP4 and CFTR in the regulation of cAMP and β-adrenergic contraction in cardiac myocytes.European journal of pharmacology · 2012Article
- Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells.American journal of physiology. Cell physiology · 2012Article
- Specific PI3K isoform modulation in heart failure: lessons from transgenic mice.Current heart failure reports · 2011Review
- Compartmentalization of beta-adrenergic signals in cardiomyocytes.Circulation research · 2011Review
- cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium.The Journal of pharmacology and experimental therapeutics · 2009Article
- Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics.Pharmacology & therapeutics · 2009Review
- Supramolecular assemblies and localized regulation of voltage-gated ion channels.Physiological reviews · 2009Review
- 5-HT4-elicited positive inotropic response is mediated by cAMP and regulated by PDE3 in failing rat and human cardiac ventricles.British journal of pharmacology · 2008Article
- beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.The Journal of clinical investigation · 2008Article
- Alveolar epithelial beta2-adrenergic receptors.American journal of respiratory cell and molecular biology · 2008Review
- Compartmentation of cAMP signaling in cardiac myocytes: a computational study.Biophysical journal · 2007Article
- cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes.The Journal of physiology · 2007Article
- Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart.Circulation research · 2007Review
- Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells.American journal of physiology. Cell physiology · 2007Article
- PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases.The Journal of cell biology · 2006Article
- Kinetics of ion channel modulation by cAMP in rat hippocampal neurones.The Journal of physiology · 2006Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of cyclic nucleotide phosphodiesterase (PDE) isoforms in the beta2-adrenergic stimulation of the L-type Ca2+ current (ICa,L) was investigated in frog ventricular myocytes using double patch-clamp and double-barrelled microperfusion techniques. Isoprenaline (ISO, 1 nM to 10 microM) was applied on one half of the cell, either alone or in the presence of PDE inhibitors, and the local and distant responses of ICa,L were used to determine the gradient of local vs. distant cAMP concentration (alpha). IBMX (100 microM), a non-selective PDE inhibitor, reduced alpha from 40 to 4.4 indicating a 9-fold reduction in intracellular cAMP compartmentation when all PDE activity was blocked. While PDE1 and PDE2 inhibition had no effect, PDE3 inhibition by milrinone (3 microM) or PDE4 inhibition by Ro 20-1724 (3 microM) reduced alpha by 6- and 4-fold, respectively. A simultaneous application of milrinone and Ro 20-1724 produced a similar effect to IBMX, showing that PDE3 and PDE4 were the major PDEs accounting for cAMP compartmentation. Okadaic acid (3 microM), a non-selective phosphatase inhibitor, or H89 (1 microM), an inhibitor of cAMP-dependent protein kinase (PKA), had no effect on the distant response of ICa,L to ISO indicating that PDE activation by PKA played a minor role in cAMP compartmentation. Our results demonstrate that PDE activity determines the degree of cAMP compartmentation in frog ventricular cells upon beta2-adrenergic stimulation. PDE3 and PDE4 subtypes play a major role in this process, and contribute equally to ensure a functional coupling of beta2-adrenergic receptors with nearby Ca2+ channels via local elevations of cAMP.
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