Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats
The mechanisms underlying the generation of febrile seizures are poorly understood. We suggest that high temperature contributes to febrile seizures and specifically tested the hypothesis that hyperthermia suppressed GABAA-receptor-mediated inhibition in hippocampal neurons using whole-cell patch cl...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-09-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610700112X |
| _version_ | 1830088873273720832 |
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| author | Lintao Qu Xinhuai Liu Chiping Wu L. Stan Leung |
| author_facet | Lintao Qu Xinhuai Liu Chiping Wu L. Stan Leung |
| author_sort | Lintao Qu |
| collection | DOAJ |
| description | The mechanisms underlying the generation of febrile seizures are poorly understood. We suggest that high temperature contributes to febrile seizures and specifically tested the hypothesis that hyperthermia suppressed GABAA-receptor-mediated inhibition in hippocampal neurons using whole-cell patch clamp recordings. We found that heating from a baseline temperature of 32 °C to 40 °C suppressed the peak amplitude of GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) by 50±4.7% and decreased the decay time constant of IPSCs by 60.6±6.7% in immature CA1 neurons in the rat hippocampus. This inhibitory effect partly results from reduced IPSC conductance and increased GABA uptake, as demonstrated by the fact that GABA uptake blocker N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (SKF89976A) significantly reduced the peak suppression and decay time decrease of the IPSC during hyperthermia. In addition, hyperthermia (40 °C) produced a significantly larger depression of the IPSC peak than the slope or peak of the excitatory postsynaptic current (EPSC), and IPSCs recovered slower than EPSCs after hyperthermia. The larger decrease in GABAA-receptor-mediated inhibition during and after hyperthermia, as compared with excitation, may shift the excitation/inhibition balance and contribute to the generation of febrile seizures. |
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| format | Article |
| id | doaj.art-9b81d204f7314990826fa00aef073d6b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:34:41Z |
| publishDate | 2007-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-9b81d204f7314990826fa00aef073d6b2022-12-21T22:24:30ZengElsevierNeurobiology of Disease1095-953X2007-09-01273320327Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature ratsLintao Qu0Xinhuai Liu1Chiping Wu2L. Stan Leung3Graduate Program in Neuroscience, University of Western Ontario, London, CanadaDepartment of Clinical Neurological Science, University of Western Ontario, London, Canada; Department of Physiology and Pharmacology, Medical Science Building, University of Western Ontario, London, Ontario, Canada N6A 5C1Toronto Western Research Institute, University Health Network, Toronto, CanadaGraduate Program in Neuroscience, University of Western Ontario, London, Canada; Department of Clinical Neurological Science, University of Western Ontario, London, Canada; Department of Physiology and Pharmacology, Medical Science Building, University of Western Ontario, London, Ontario, Canada N6A 5C1; Corresponding author. Department of Physiology and Pharmacology, Medical Science Building, University of Western Ontario, London, Ontario, Canada N6A 5C1. Fax: +1 519 661 3827.The mechanisms underlying the generation of febrile seizures are poorly understood. We suggest that high temperature contributes to febrile seizures and specifically tested the hypothesis that hyperthermia suppressed GABAA-receptor-mediated inhibition in hippocampal neurons using whole-cell patch clamp recordings. We found that heating from a baseline temperature of 32 °C to 40 °C suppressed the peak amplitude of GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) by 50±4.7% and decreased the decay time constant of IPSCs by 60.6±6.7% in immature CA1 neurons in the rat hippocampus. This inhibitory effect partly results from reduced IPSC conductance and increased GABA uptake, as demonstrated by the fact that GABA uptake blocker N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (SKF89976A) significantly reduced the peak suppression and decay time decrease of the IPSC during hyperthermia. In addition, hyperthermia (40 °C) produced a significantly larger depression of the IPSC peak than the slope or peak of the excitatory postsynaptic current (EPSC), and IPSCs recovered slower than EPSCs after hyperthermia. The larger decrease in GABAA-receptor-mediated inhibition during and after hyperthermia, as compared with excitation, may shift the excitation/inhibition balance and contribute to the generation of febrile seizures.http://www.sciencedirect.com/science/article/pii/S096999610700112XGABAInhibitionExcitationUptakeIPSCEPSC |
| spellingShingle | Lintao Qu Xinhuai Liu Chiping Wu L. Stan Leung Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats Neurobiology of Disease GABA Inhibition Excitation Uptake IPSC EPSC |
| title | Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats |
| title_full | Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats |
| title_fullStr | Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats |
| title_full_unstemmed | Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats |
| title_short | Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats |
| title_sort | hyperthermia decreases gabaergic synaptic transmission in hippocampal neurons of immature rats |
| topic | GABA Inhibition Excitation Uptake IPSC EPSC |
| url | http://www.sciencedirect.com/science/article/pii/S096999610700112X |
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