ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Auxiliary α2δ1 and α2δ3 Subunits of Calcium Channels Drive Excitatory and Inhibitory Neuronal Network Development.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury-associated immunodepression syndrome.Neural regeneration research · 2026Article
- Synaptic Ca2+ channels and neurexins are linked through direct and indirect binding complexes.Scientific reports · 2026Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.Genetics · 2025Article
- Mesenchymal stromal cell secretome-induced synaptogenesis is mediated by thrombospondin-1.iScience · 2025Article
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.bioRxiv : the preprint server for biology · 2025Article
- Presynaptic αNeuron · 2025Article
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- Fibroblast reprogramming in the dura mater of NTG-induced migraine-related chronic hypersensitivity model drives monocyte infiltration via Angptl1-dependent stromal signaling.The journal of headache and pain · 2025Article
- The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.Molecular neurobiology · 2025Review
- Harnessing Deep Learning Methods for Voltage-Gated Ion Channel Drug Discovery.Physiology (Bethesda, Md.) · 2025Review
- The VGCC auxiliary subunit α2δ1 is an extracellular GluA1 interactor and regulates LTP, spatial memory, and seizure susceptibility.bioRxiv : the preprint server for biology · 2024Article
- Autism-Linked Mutations in αPharmaceuticals (Basel, Switzerland) · 2024Article
- α2δ1-mediated maladaptive sensory plasticity disrupts adipose tissue homeostasis following spinal cord injury.Cell reports. Medicine · 2024Article
- The importance of cache domains in αChannels (Austin, Tex.) · 2023Article
- Pathophysiological Roles of Auxiliary Calcium Channel αHandbook of experimental pharmacology · 2023Article
- Involvement of CaThe Journal of physiology · 2022Article
- Effect of gabapentin on neurogenesis in hippocampal dentate gyrus of adult rats with co-disease of chronic pain and depression.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Impact of In Utero Exposure to Antiepileptic Drugs on Neonatal Brain Function.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Tripartite synaptomics: Cell-surface proximity labeling in vivo.Neuroscience research · 2021Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
VGCCs are multisubunit complexes that play a crucial role in neuronal signaling. Auxiliary α2δ subunits of VGCCs modulate trafficking and biophysical properties of the pore-forming α1 subunit and trigger excitatory synaptogenesis. Alterations in the expression level of α2δ subunits were implicated in several syndromes and diseases, including chronic neuropathic pain, autism, and epilepsy. However, the contribution of distinct α2δ subunits to excitatory/inhibitory imbalance and aberrant network connectivity characteristic for these pathologic conditions remains unclear. Here, we show that α2δ1 overexpression enhances spontaneous neuronal network activity in developing and mature cultures of hippocampal neurons. In contrast, overexpression, but not downregulation, of α2δ3 enhances neuronal firing in immature cultures, whereas later in development it suppresses neuronal activity. We found that α2δ1 overexpression increases excitatory synaptic density and selectively enhances presynaptic glutamate release, which is impaired on α2δ1 knockdown. Overexpression of α2δ3 increases the excitatory synaptic density as well but also facilitates spontaneous GABA release and triggers an increase in the density of inhibitory synapses, which is accompanied by enhanced axonaloutgrowth in immature interneurons. Together, our findings demonstrate that α2δ1 and α2δ3 subunits play distinct but complementary roles in driving formation of structural and functional network connectivity during early development. An alteration in α2δ surface expression during critical developmental windows can therefore play a causal role and have a profound impact on the excitatory-to-inhibitory balance and network connectivity.
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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.