ArticleProceedings of the National Academy of Sciences of the United States of America2004
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Direct energy consumption by inhibitory GABAFrontiers in neuroscience · 2026Article
- Temporal characterisation and electrophysiological implications of TBI-induced serine/threonine kinase activity in mouse cortex.Cellular and molecular life sciences : CMLS · 2025Article
- Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.Membranes · 2024Article
- GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.Life (Basel, Switzerland) · 2022Article
- GABAScientific reports · 2022Article
- Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs.Cell death & disease · 2021Article
- Dissecting the Molecular Determinants of GABABrain sciences · 2021Article
- Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?International journal of molecular sciences · 2020Review
- Neurobiological Correlates of Alpha-Tocopherol Antiepileptogenic Effects and MicroRNA Expression Modulation in a Rat Model of Kainate-Induced Seizures.Molecular neurobiology · 2018Article
- Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin.Epilepsia open · 2016Article
- Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy.Frontiers in cellular neuroscience · 2013Article
- Loss of functional GABA(A) receptors in the Alzheimer diseased brain.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Functional rundown of gamma-aminobutyric acid(A) receptors in human hypothalamic hamartomas.Annals of neurology · 2011Article
- Enhancement of GABA(A)-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- GABA(A) receptor properties in catastrophic infantile epilepsy.Epilepsy research · 2008Article
- Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Microtransplantation of neurotransmitter receptors from postmortem autistic brains to Xenopus oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Oxidative stress evokes a metabolic adaptation that favors increased NADPH synthesis and decreased NADH production in Pseudomonas fluorescens.Journal of bacteriology · 2007Article
Corrections and comments
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14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The properties of gamma-aminobutyric acid (GABA) type A receptors (GABA(A) receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABA(A) receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat alpha 1 beta 2 gamma 2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABA(A) receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABA(A) receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABA(A)-receptor beta 1, beta 2, beta 3, and gamma 2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABA(A) receptors. Blockage of phosphatases stabilizes the TLE GABA(A) receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy.
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