ArticleNeuropharmacology2016
Convergent phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache.Brain : a journal of neurology · 2026Article
- G Protein-Coupled Receptors in Cerebrovascular Diseases: Signaling Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Ethnopharmacological relevance of Chinese medicinal materials and natural products in epilepsy: a critical multi-target review integrating neurons, glia and inflammatory signaling.Frontiers in pharmacology · 2026Review
- Gene and Allele-Specific Expression Underlying the Electric Signal Divergence in African Weakly Electric Fish.Molecular biology and evolution · 2024Article
- PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.Acta pharmacologica Sinica · 2023Article
- Music with Different Tones Affects the Development of Brain Nerves in Mice in Early Life through BDNF and Its Downstream Pathways.International journal of molecular sciences · 2023Article
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
- Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status.International journal of molecular sciences · 2021Review
- Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.Aging and disease · 2020Review
- Pituitary adenylate cyclase-activating polypeptide-induced PAC1 receptor internalization and recruitment of MEK/ERK signaling enhance excitability of dentate gyrus granule cells.American journal of physiology. Cell physiology · 2020Article
- The Role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in the Hippocampal Dentate Gyrus.Frontiers in cellular neuroscience · 2020Article
- Parallel signaling pathways of pituitary adenylate cyclase activating polypeptide (PACAP) regulate several intrinsic ion channels.Annals of the New York Academy of Sciences · 2019Review
- PACAP-Induced PAC1 Receptor Internalization and Recruitment of Endosomal Signaling Regulate Cardiac Neuron Excitability.Journal of molecular neuroscience : MN · 2019Review
- Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Hippocampal Synaptic Transmission and Plasticity: New Therapeutic Suggestions for Fragile X Syndrome.Frontiers in cellular neuroscience · 2019Review
- Angiotensin II Triggers Peripheral Macrophage-to-Sensory Neuron Redox Crosstalk to Elicit Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- ERK5 Phosphorylates KInternational journal of molecular sciences · 2018Article
- β-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.PloS one · 2018Article
- Saikosaponin A modulates remodeling of Kv4.2-mediated A-type voltage-gated potassium currents in rat chronic temporal lobe epilepsy.Drug design, development and therapy · 2018Article
- TRPC6-mediated ERK1/2 Activation Regulates Neuronal Excitability via Subcellular Kv4.3 Localization in the Rat Hippocampus.Frontiers in cellular neuroscience · 2017Article
- Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability.American journal of physiology. Cell physiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The endogenous neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is secreted by both neuronal and non-neuronal cells in the brain and spinal cord, in response to pathological conditions such as stroke, seizures, chronic inflammatory and neuropathic pain. PACAP has been shown to exert various neuromodulatory and neuroprotective effects. However, direct influence of PACAP on the function of intrinsically excitable ion channels that are critical to both hyperexcitation as well as cell death, remain largely unexplored. The major dendritic K(+) channel Kv4.2 is a critical regulator of neuronal excitability, back-propagating action potentials in the dendrites, and modulation of synaptic inputs. We identified, cloned and characterized the downstream signaling originating from the activation of three PACAP receptor (PAC1) isoforms that are expressed in rodent hippocampal neurons that also exhibit abundant expression of Kv4.2 protein. Activation of PAC1 by PACAP leads to phosphorylation of Kv4.2 and downregulation of channel currents, which can be attenuated by inhibition of either PKA or ERK1/2 activity. Mechanistically, this dynamic downregulation of Kv4.2 function is a consequence of reduction in the density of surface channels, without any influence on the voltage-dependence of channel activation. Interestingly, PKA-induced effects on Kv4.2 were mediated by ERK1/2 phosphorylation of the channel at two critical residues, but not by direct channel phosphorylation by PKA, suggesting a convergent phosphomodulatory signaling cascade. Altogether, our findings suggest a novel GPCR-channel signaling crosstalk between PACAP/PAC1 and Kv4.2 channel in a manner that could lead to neuronal hyperexcitability.
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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.