ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Dynamics of protein kinase A signaling at the membrane, in the cytosol, and in the nucleus of neurons in mouse brain slices.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner.Scientific reports · 2024Article
- Molecular Adaptations of BDNF/NT-4 Neurotrophic and Muscarinic Pathways in Ageing Neuromuscular Synapses.International journal of molecular sciences · 2024Article
- GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses.Molecular psychiatry · 2024Article
- Activity of Protein Kinase A in the Frontal Cortex in Schizophrenia.Brain sciences · 2023Article
- A Role for Second Messengers in Axodendritic Neuronal Polarity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens.The Journal of physiology · 2022Article
- Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.Journal of neuroscience methods · 2021Review
- PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice.Communications biology · 2021Article
- Combined Optogenetic Approaches Reveal Quantitative Dynamics of Endogenous Noradrenergic Transmission in the Brain.iScience · 2020Article
- Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity.EMBO reports · 2020Article
- Article
- Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.The Journal of physiology · 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
- Article
- Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation.Neurobiology of learning and memory · 2017Article
- Dendritic geometry shapes neuronal cAMP signalling to the nucleus.Nature communications · 2015Article
- GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia.Neuron · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cAMP-dependent protein kinase A (PKA) plays a ubiquitous role in the regulation of neuronal activity, but the dynamics of its activation have been difficult to investigate. We used the genetically encoded fluorescent probe AKAR2 to record PKA activation in the cytosol and the nucleus of neurons in mouse brain slice preparations, whereas the potassium current underlying the slow afterhyperpolarization potential (sAHP) in thalamic intralaminar neurons was used to monitor PKA activation at the membrane. Adenylyl cyclase was stimulated either directly using forskolin or via activation of 5-HT7 receptors. Both stimulations produced a maximal effect on sAHP, whereas in the cytosol, the amplitude of the 5-HT7 receptor-mediated response was half of that after direct adenylyl cyclase stimulation with forskolin. 5-HT7-mediated PKA responses were obtained in 30 s at the membrane, in 2.5 min in the cytosol, and in 13 min in the nucleus. Our results show in morphologically intact mammalian neurons the potential physiological relevance of PKA signal integration at the subcellular level: neuromodulators produce fast and powerful effects on membrane excitability, consistent with a highly efficient functional coupling between adenylyl cyclases, PKA, and target channels. Phosphorylation in the cytosol is slower and of graded amplitude, showing a differential integration of the PKA signal between the membrane and the cytosol. The nucleus integrates these cytosolic signals over periods of tens of minutes, consistent with passive diffusion of the free catalytic subunit of PKA into the nucleus, eventually resulting in a graded modulation of gene expression.
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Registered trials
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