ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Somatostatin receptor subtype 4 couples to the M-current to regulate seizures.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- The Primary Cilia are Associated with the Axon Initial Segment in Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025Review
- Reciprocal chromosome translocation t(3;4)(q27;q31.2) with deletion of 3q27 and reduced FBXW7 expression in a patient with developmental delay, hypotonia, and seizures.Journal of human genetics · 2024Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Elucidation of the binding mode of organic polysulfides on the human TRPA1 receptor.Frontiers in physiology · 2023Article
- Reassessment of SST4 Somatostatin Receptor Expression Using SST4-eGFP Knockin Mice and the Novel Rabbit Monoclonal Anti-Human SST4 Antibody 7H49L61.International journal of molecular sciences · 2021Article
- Synthesis and structure-activity relationships of 3,4,5-trisubstituted-1,2,4-triazoles: high affinity and selective somatostatin receptor-4 agonists for Alzheimer's disease treatment.RSC medicinal chemistry · 2021Article
- Somatostatin, a Presynaptic Modulator of Glutamatergic Signal in the Central Nervous System.International journal of molecular sciences · 2021Review
- Human Somatostatin SSTInternational journal of molecular sciences · 2021Article
- Somatostatin expressing GABAergic interneurons in the medial entorhinal cortex preferentially inhibit layerCommunications biology · 2020Article
- Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains.International journal of molecular sciences · 2020Article
- Novel Drug-Like Somatostatin Receptor 4 Agonists are Potential Analgesics for Neuropathic Pain.International journal of molecular sciences · 2019Article
- Molecular and Cellular Mechanisms Underlying Somatostatin-Based Signaling in Two Model Neural Networks, the Retina and the Hippocampus.International journal of molecular sciences · 2019Review
- Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence.Frontiers in behavioral neuroscience · 2019Article
- Presynaptic Mechanisms and KCNQ Potassium Channels Modulate Opioid Depression of Respiratory Drive.Frontiers in physiology · 2019Article
- Discovery of a 3,4,5-trisubstituted-1,2,4-triazole agonist with high affinity and selectivity at the somatostatin subtype-4 (sstMedChemComm · 2018Article
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain.Frontiers in pharmacology · 2018Article
- Somatostatin depresses the excitability of subicular bursting cells: Roles of inward rectifier KHippocampus · 2017Article
- Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity.Developmental cell · 2017Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The K(+) M-current (I(M), Kv7) is an important regulator of cortical excitability, and mutations in these channels cause a seizure disorder in humans. The neuropeptide somatostatin (SST), which has antiepileptic properties, augments I(M) in hippocampal CA1 pyramidal neurons. We used SST receptor knock-out mice and subtype-selective ligands to investigate the receptor subtype that couples to I(M) and mediates the antiepileptic effects of SST. Using pentylenetetrazole as a chemoconvulsant, SST(2), SST(3), and SST(4) receptor knock-out mice all had shorter latencies to different seizure stages and increased seizure severity when compared with wild-type mice. However, the most robust differences were observed in the SST(4) knock-outs. When seizures were induced by systemic injection of kainate, only SST(4) knock-outs showed an increase in seizure sensitivity. We next examined the action of SST and subtype-selective SST agonists on electrophysiological parameters in hippocampal slices of wild-type and receptor knock-out mice. SST(2) and SST(4) appear to mediate the majority of SST inhibition of epileptiform activity in CA1. SST lacked presynaptic effects in mouse CA1, in contrast to our previous findings in rat. SST increased I(M) in CA1 pyramidal neurons of wild-type and SST(2) knock-out mice, but not SST(4) knock-out mice. Using M-channel blockers, we found that SST(4) coupling to M-channels is critical to its inhibition of epileptiform activity. This is the first demonstration of an endogenous enhancer of I(M) that is important in controlling seizure activity. SST(4) receptors could therefore be an important novel target for developing new antiepileptic and antiepileptogenic drugs.
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