ArticleProceedings of the National Academy of Sciences of the United States of America2007
GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 68 citations in OpenAlex.
- Epilepsy and exercise: a narrative review on the crucial role of neurosteroids in modulating GABAergic neurotransmission.Brain communications · 2026Review
- Direct energy consumption by inhibitory GABAFrontiers in neuroscience · 2026Article
- Transcriptomic and electrophysiological alterations underlying phenotypic variability in SCN1A-associated febrile seizures.Scientific reports · 2025Article
- α4β2The Journal of physiology · 2025Article
- Erythropoietin for Seizures and Epilepsy: Neuroprotective Effects, Mechanisms, and Contradictory Risks.CNS & neurological disorders drug targets · 2025Review
- Histamine HPharmacology research & perspectives · 2024Article
- Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.Membranes · 2024Article
- The Possible Role of Brain-derived Neurotrophic Factor in Epilepsy.Neurochemical research · 2024Review
- In the fast lane: Receptor trafficking during status epilepticus.Epilepsia open · 2023Review
- GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.Life (Basel, Switzerland) · 2022Article
- Review
- Microtransplantation of Synaptic Membranes to Reactivate Human Synaptic Receptors for Functional Studies.Journal of visualized experiments : JoVE · 2022Article
- Human iPSC Modeling of Genetic Febrile Seizure Reveals Aberrant Molecular and Physiological Features Underlying an Impaired Neuronal Activity.Biomedicines · 2022Article
- Molecular Targets of Cannabinoids Associated with Depression.Current medicinal chemistry · 2022Review
- Physiological role for GABANature communications · 2021Article
- Dissecting the Molecular Determinants of GABABrain sciences · 2021Article
- Alpha adrenergic receptor signaling in the hypothalamic paraventricular nucleus is diminished by the chronic intermittent hypoxia model of sleep apnea.Experimental neurology · 2021Article
- Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?International journal of molecular sciences · 2020Review
- Use and Future Prospects of in Vivo Microdialysis for Epilepsy Studies.ACS chemical neuroscience · 2019Review
- The Functional Role of Spontaneously Opening GABAFrontiers in molecular neuroscience · 2019Article
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A study was made of the "rundown" of GABA(A) receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABA(A) receptors. Upon repetitive activation with GABA (1 mM), "epileptic" GABA(A) receptors exhibited a GABA(A)-current (I(GABA)) rundown that was significantly enhanced by Zn(2+) (</=250 microM), and practically abolished by the high-affinity GABA(A) receptor inverse agonist SR95531 (gabazine; 2.5-25 microM). Conversely, I(GABA) generated by "control" GABA(A) receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn(2+). We conclude that rundown of mTLE epileptic receptors depends on the presence of "phasic GABA(A) receptors" that have low sensitivity to antagonism by Zn(2+). Additionally, we found that GABA(A) receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn(2+) (40 microM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABA(A) receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABA(A) receptor activity may represent a useful therapeutic approach to the disease.
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