ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Type 4 phosphodiesterase plays different integrating roles in different cellular domains in pyramidal cortical neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 74 citations in OpenAlex.
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- A Role for Second Messengers in Axodendritic Neuronal Polarity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.Journal of neuroscience methods · 2021Review
- Combined Optogenetic Approaches Reveal Quantitative Dynamics of Endogenous Noradrenergic Transmission in the Brain.iScience · 2020Article
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Discovery, Radiolabeling, and Evaluation of Subtype-Selective Inhibitors for Positron Emission Tomography Imaging of Brain Phosphodiesterase-4D.ACS chemical neuroscience · 2020Article
- Genetic Association of Phosphodiesterases With Human Cognitive Performance.Frontiers in molecular neuroscience · 2019Review
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.The Journal of physiology · 2017Article
- Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast.Experimental neurology · 2017Article
- Interrogating cyclic AMP signaling using optical approaches.Cell calcium · 2017Review
- Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates.Cell reports · 2017Article
- AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons.Nature chemical biology · 2017Article
- Signaling: Spatial regulation of axonal cAMP.Nature chemical biology · 2017Article
- Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation.Neurobiology of learning and memory · 2017Article
- cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons.Cell reports · 2016Article
- A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors.Nature communications · 2016Article
- Activation of α7 nicotinic acetylcholine receptors increases intracellular cAMP levels via activation of AC1 in hippocampal neurons.Neuropharmacology · 2015Article
- Dendritic geometry shapes neuronal cAMP signalling to the nucleus.Nature communications · 2015Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated the role of phosphodiesterases (PDEs) in the integration of cAMP signals and protein kinase A (PKA) activity following beta-adrenergic stimulation, by carrying out real-time imaging of male mouse pyramidal cortical neurons expressing biosensors to monitor cAMP levels (Epac1-camps and Epac2-camps300) or PKA activity (AKAR2). In the soma, isoproterenol (ISO) increased the PKA signal to approximately half the maximal response obtained with forskolin, with a characteristic beta(1) pharmacology and an EC(50) of 4.5 nm. This response was related to free cAMP levels in the submicromolar range. The specific type 4 PDE (PDE4) inhibitor rolipram had a very small effect alone, but strongly potentiated the PKA response to ISO. Blockers of other PDEs had no effect. PDE4 thus acts as a brake in the propagation of the beta(1)-adrenergic signal from the membrane to the bulk somatic cytosol. The results for a submembrane domain were markedly different, whether recorded with a PKA-sensitive potassium current related to the slow AHP or by two-photon imaging of small distal dendrites. The responses to ISO were stronger than in the bulk cytosol. This is consistent with the cAMP/PKA signal being strong at the membrane, as shown by electrophysiology, and favored in cellular domains with a high surface area to volume ratio, in which this signal was detected by imaging. Rolipram alone also produced a strong cAMP/PKA signal, revealing tonic cAMP production. PDE4 thus appears as a crucial integrator with different physiological implications in different subcellular domains.
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