Qu Lintao, Liu Xinhuai, Wu Chiping, Leung L Stan
Graduate Program in Neuroscience, University of Western Ontario, London, Canada.
Neurobiol Dis. 2007 Sep;27(3):320-7. doi: 10.1016/j.nbd.2007.06.003. Epub 2007 Jun 12.
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.
发热性惊厥产生的潜在机制目前尚不清楚。我们认为高温与发热性惊厥有关，并特别检验了以下假设：使用全细胞膜片钳记录法，高温会抑制海马神经元中GABAA受体介导的抑制作用。我们发现，将大鼠海马未成熟CA1神经元的基线温度从32摄氏度加热到40摄氏度，会使GABAA受体介导的抑制性突触后电流（IPSC）的峰值幅度降低50±4.7%，并使IPSC的衰减时间常数降低60.6±6.7%。这种抑制作用部分源于IPSC电导降低和GABA摄取增加，这一事实表明，GABA摄取阻滞剂N-(4,4-二苯基-3-丁烯基)-3-哌啶羧酸（SKF89976A）在高温期间显著降低了IPSC的峰值抑制和衰减时间减少。此外，高温（40摄氏度）对IPSC峰值的抑制作用明显大于兴奋性突触后电流（EPSC）的斜率或峰值，并且高温后IPSC的恢复比EPSC慢。与兴奋相比，高温期间和之后GABAA受体介导的抑制作用的更大降低可能会改变兴奋/抑制平衡，并导致发热性惊厥的发生。
