ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Systematic review: The relationship between gabapentinoids, etizolam, and drug related deaths in Scotland.PloS one · 2024Pooled it
- Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale.Molecular psychiatry · 2022Pooled it
- Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain.International journal of molecular sciences · 2026Review
- Gabapentin-Induced Hypoglycemia in a Patient With Pre-Diabetes: A Case Report and Review of the Literature.Clinical case reports · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Protective Effects of Melatonin and Bee Pollen on Hematotoxicity and Hepatorenal Toxicity Induced by Long-Term Intake of Gabapentin in Female Albino Rats.Cell biochemistry and biophysics · 2025Article
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Voltage-Gated Calcium Channels Play a Central Role in Caenorhabditis elegans Response to Noxious Heat.Neurochemical research · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Structural biology of voltage-gated calcium channels.Channels (Austin, Tex.) · 2024Review
- Rat Sympathetic Neuron Calcium Channels Are Insensitive to Gabapentin.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanism of gabapentinoid potentiation of opioid effects on cyclic AMP signaling in neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The importance of cache domains in αChannels (Austin, Tex.) · 2023Article
- Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1.Molecular brain · 2023Article
- Gabapentin-Associated Movement Disorders: A Literature Review.Medicines (Basel, Switzerland) · 2023Review
- Active Zone Trafficking of CaV2/UNC-2 Channels Is Independent of β/CCB-1 and α2δ/UNC-36 Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Fighting pain: the structure of gabapentin and its binding site in the CaNature structural & molecular biology · 2023Article
- Structural basis for CaNature structural & molecular biology · 2023Article
- Pregabalin Use/Misuse: A Source of Consternation in Western Punjab.Indian journal of psychological medicine · 2023Article
- Conserved but not critical: Trafficking and function of NaFrontiers in molecular neuroscience · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The α2δ subunits of voltage-gated calcium channels are important modulatory subunits that enhance calcium currents and may also have other roles in synaptogenesis. The antiepileptic and antiallodynic drug gabapentin (GBP) binds to the α2δ-1 and α2δ-2 isoforms of this protein, and its binding may disrupt the binding of an endogenous ligand, required for their correct function. We have shown previously that GBP produces a chronic inhibitory effect on calcium currents by causing a reduction in the total number of α2δ and α1 subunits at the cell surface. This action of GBP is likely to be attributable to a disruption of the trafficking of α2δ subunits, either to or from the plasma membrane. We studied the effect of GBP on the internalization of, and insertion into the plasma membrane of α2δ-2 using an α-bungarotoxin binding site-tagged α2δ-2 subunit, and a fluorescent derivative of α-bungarotoxin. We found that GBP specifically disrupts the insertion of α2δ-2 from post-Golgi compartments to the plasma membrane, and this effect was prevented by a mutation of α2δ-2 that abolishes its binding to GBP. The coexpression of the GDP-bound Rab11 S25N mutant prevented the GBP-induced decrease in α2δ-2 cell surface levels, both in cell lines and in primary neurons, and the GBP-induced reduction in calcium channel currents. In contrast, the internalization of α2δ-2 was unaffected by GBP. We conclude that GBP acts by preventing the recycling of α2δ-2 from Rab11-positive recycling endosomes to the plasma membrane.
Indexed as
Identifiers
What OpenQuestion holds
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.