ArticleThe Journal of physiology2001
Diminished allopregnanolone enhancement of GABA(A) receptor currents in a rat model of chronic temporal lobe epilepsy.
Article in The Journal of physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 71 citations in OpenAlex.
- Status epilepticus: Updates on mechanisms and treatments.Epilepsia open · 2025Review
- Article
- Human Microglia Synthesize Neurosteroids to Cope with Rotenone-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Progesterone modulates neuronal excitability bidirectionally.Neuroscience letters · 2021Review
- Reduced neurosteroid potentiation of GABAAnnals of clinical and translational neurology · 2020Article
- Neurosteroid regulation of GABABrain research · 2019Review
- Catamenial-like seizure exacerbation in mice with targeted ablation of extrasynaptic δGABA-a receptors in the brain.Journal of neuroscience research · 2017Article
- Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Normal and epilepsy-associated pathologic function of the dentate gyrus.Progress in brain research · 2016Review
- PKCε and allopregnanolone: functional cross-talk at the GABAA receptor level.Frontiers in cellular neuroscience · 2015Article
- Limbic networks and epileptiform synchronization: the view from the experimental side.International review of neurobiology · 2014Review
- N-methyl-D-aspartic acid receptor activation downregulates expression of δ subunit-containing GABAA receptors in cultured hippocampal neurons.Molecular pharmacology · 2013Article
- GABAergic transmission in temporal lobe epilepsy: the role of neurosteroids.Experimental neurology · 2013Review
- Role of hormones and neurosteroids in epileptogenesis.Frontiers in cellular neuroscience · 2013Article
- A mouse kindling model of perimenstrual catamenial epilepsy.The Journal of pharmacology and experimental therapeutics · 2012Article
- Hilar mossy cells of the dentate gyrus: a historical perspective.Frontiers in neural circuits · 2012Article
- Receptors with low affinity for neurosteroids and GABA contribute to tonic inhibition of granule cells in epileptic animals.Neurobiology of disease · 2010Article
- Endogenous neurosteroid synthesis modulates seizure frequency.Annals of neurology · 2010Article
- Enhanced tonic GABA current in normotopic and hilar ectopic dentate granule cells after pilocarpine-induced status epilepticus.Journal of neurophysiology · 2009Article
- Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
1. Neurosteroid modulation of GABA(A) receptors present on dentate granule cells (DGCs) acutely isolated from epileptic (epileptic DGCs) or control rats (control DGCs) was studied by application of GABA with or without the modulators and by measuring the amplitude of peak whole-cell currents. 2. In epileptic DGCs, GABA efficacy (1394 +/- 277 pA) was greater than in control DGCs (765 +/- 38 pA). 3. Allopregnanolone enhanced GABA-evoked currents less potently in epileptic DGCs (EC50 = 92.7 +/- 13.4 nM) than in control DGCs (EC50 = 12.9 +/- 2.3 nM). 4. Pregnenolone sulfate inhibited GABA-evoked currents with similar potency and efficacy in control and epileptic DGCs. 5. Diazepam enhanced GABA-evoked currents less potently in epileptic (EC50 = 69 +/- 14 nM) compared to the control DGCs (EC50 = 29.9 +/- 5.7 nM). 6. There were two different patterns of zolpidem modulation of GABA(A) receptor currents in the epileptic DGCs. In one group, zolpidem enhanced GABA(A) receptor currents but with reduced potency compared to the control DGCs (EC50 = 134 +/- 20 nM vs. EC50 = 52 +/- 13 nM). In the second group of epileptic DGCs zolpidem inhibited GABA(A) receptor currents, an effect not observed in control DGCs. 7. Epileptic DGCs were more sensitive to Zn2+ inhibition of GABA(A) receptor currents (IC50 = 19 +/- 6 microM) compared to control (IC50 = 94.7 +/- 7.9 microM). 8. This study demonstrates significant differences between epileptic and control DGCs. We conclude that (1) diminished sensitivity of GABA(A) receptors of epileptic DGCs to allopregnanolone can increase susceptibility to seizures; (2) reduced sensitivity to diazepam and zolpidem, and increased sensitivity to Zn2+ indicate that loss of allopregnanolone sensitivity is likely to be due to altered subunit expression of postsynaptic GABA(A) receptors present on epileptic DGCs; and (3) an inverse effect of zolpidem in some epileptic DGCs demonstrates the heterogeneity of GABA(A) receptors present on epileptic DGCs.
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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.