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 clamp recordings. We found that heating from a baseline temperature of 32 degrees C to 40 degrees 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 degrees 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.
Qu
Lintao
L
Graduate Program in Neuroscience, University of Western Ontario, London, Canada.
Liu
Xinhuai
X
Wu
Chiping
C
Leung
L Stan
LS
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005334:Fever / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D020332:Rats, Inbred LEC; D003294:Seizures, Febrile / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid