Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats

Lintao Qu; Xinhuai Liu; Chiping Wu; L. Stan Leung

Neurobiology of Disease (Sep 2007)

Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats

Lintao Qu,
Xinhuai Liu,
Chiping Wu,
L. Stan Leung

Affiliations

Lintao Qu: Graduate Program in Neuroscience, University of Western Ontario, London, Canada
Xinhuai Liu: 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
Chiping Wu: Toronto Western Research Institute, University Health Network, Toronto, Canada
L. Stan Leung: Graduate 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.

Journal volume & issue: Vol. 27, no. 3
pp. 320 – 327

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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