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 GABA boolean AND-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 GA BA boolean AND -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 CA] 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-butenyt)-3-piperidinecarboxylic acid (SKF89976A) significantly reduced the peak suppression and decay time decrease of the TPSC during hyperthermia. In addition, hyperthermin (40 degrees C) produced a significantly larger depression of the IPSC peak than the slope or peak of the excitatory postsynaptic current (EPSC), and I PSCs recovered slower than EPSCs after bypertbermia. The larger decrease in GA BA boolean AND 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. (c) 2007 Elsevier Inc. All rights reserved.