ArticleFrontiers in cellular neuroscience2013
cAMP promotes the differentiation of neural progenitor cells in vitro via modulation of voltage-gated calcium channels.
Article in Frontiers in cellular neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 72 citations in OpenAlex.
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- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Intracellular cAMP signaling-induced CaPflugers Archiv : European journal of physiology · 2025Article
- Neuronal SLC39A8 deficiency impairs cerebellar development by altering manganese homeostasis.JCI insight · 2024Article
- Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury.International journal of molecular sciences · 2024Article
- Functional analysis and transcriptome profile of meninges and skin fibroblasts from human-aged donors.Cell proliferation · 2024Article
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- Biallelic loss-of-function variants in CACHD1 cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
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- In Vitro Simulated Neuronal Environmental Conditions Qualify Umbilical Cord Derived Highly Potent Stem Cells for Neuronal Differentiation.Stem cell reviews and reports · 2023Article
- Role of the adenylate cyclase/cyclic AMP pathway in oxytocin-induced lacrimal gland myoepithelial cells contraction.Experimental eye research · 2023Article
- TGFβ3, dibutyryl cAMP and a notch inhibitor modulate phenotype late in stem cell-derived dopaminergic neuron maturation.Frontiers in cell and developmental biology · 2023Article
- Urine-derived stem cells in neurological diseases: current state-of-the-art and future directions.Frontiers in molecular neuroscience · 2023Review
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- Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells.Molecular psychiatry · 2022Article
- A narrative review of converging evidence addressing developmental toxicity of pyrethroid insecticides.Critical reviews in toxicology · 2022Review
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanisms underlying the differentiation of neural progenitor cells (NPCs) remain poorly understood. In this study we investigated the role of Ca(2+) and cAMP (cyclic adenosine monophosphate) in the differentiation of NPCs extracted from the subventricular zone of E14.5 rat embryos. Patch clamp recordings revealed that increasing cAMP-signaling with Forskolin or IBMX (3-isobutyl-1-methylxantine) significantly facilitated neuronal functional maturation. A continuous application of IBMX to the differentiation medium substantially increased the functional expression of voltage-gated Na(+) and K(+) channels, as well as neuronal firing frequency. Furthermore, we observed an increase in the frequency of spontaneous synaptic currents and in the amplitude of evoked glutamatergic and GABAergic synaptic currents. The most prominent acute effect of applying IBMX was an increase in L-type Ca(2+)currents. Conversely, blocking L-type channels strongly inhibited dendritic outgrowth and synapse formation even in the presence of IBMX, indicating that voltage-gated Ca(2+) influx plays a major role in neuronal differentiation. Finally, we found that nifedipine completely blocks IBMX-induced CREB phosphorylation (cAMP-response-element-binding protein), indicating that the activity of this important transcription factor equally depends on both enhanced cAMP and voltage-gated Ca(2+)-signaling. Taken together, these data indicate that the up-regulation of voltage-gated L-type Ca(2+)-channels and early electrical excitability are critical steps in the cAMP-dependent differentiation of SVZ-derived NPCs into functional neurons. To our knowledge, this is the first demonstration of the acute effects of cAMP on voltage-gated Ca(+2)channels in NPC-derived developing neurons.
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