Han Ying, Qin Jiong, Bu Ding-fang, Chang Xing-zhi, Yang Zhi-xian
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Zhonghua Er Ke Za Zhi. 2006 Jul;44(7):527-30.
Febrile seizure (FS) is closely related to an altered transmission of gamma-aminobutyric acid (GABA). GABA exerts its effects through ionotropic receptors (GABA(AR) and GABA(CR)) and metabotropic receptors (GABA(BR)). GABA(BRs) are located at pre- and postsynaptic sites. Stimulation of postsynaptic receptors generates long-lasting inhibitory postsynaptic potentials (IPSPs) that are important for the fine-tuning of inhibitory neurotransmission and caused by an increase in K(+) conductance. At presynaptic sites, GABA(BRs) mediate a suppression on the release of neurotransmitters such as of GABA or glutamate by inhibiting voltage-sensitive Ca(2+) channels. The present study aimed to explore the long-term changes of GABA(B) receptor subunits in immature rats after recurrent febrile seizures.
Rats were randomly divided into control group and hyperthermia treatment group. The control rats (n = 64) were put into 37 degrees C water for 5 minutes. Rats with hyperthermia treatment were put into 44.8 degrees C water for 5 minutes. If a rat in hyperthermia treatment group showed seizure within 5 min, the rat was taken out of the water as soon as the seizure occurred. Water-immersion was carried out 10 times, once every 2 days. Rats showing 10 seizures (FS(10), n = 64) were studied. Rats exposed to hyperthermia for 10 times without seizure were also studied as hyperthermia-only (H, n = 64) group. Rats showing one seizure at the last time of 10 times of hyperthermia treatment were studied as one-seizure group (FS(1), n = 64). The other rats were studied for other research. The changes of GABA(B)R(1) and GABA(B)R(2) co-localization were detected by double fluorescence;the quantitative alteration of GABA(B)R(1) and GABA(B)R(2) were detected by quantitative RT-PCR; the binding of GABA(B)R(2) to GABA(B)R(1) was detected by immunoprecipitation/Western blot.
GABA(B)R(1), GABA(B)R(2), and the binding of GABA(B)R(2) to GABA(B)R(1) decreased after the last febrile seizure in FS(10) group, the expression of GABA(B)R(1) returned to normal in later phase while GABA(B)R(2) and the binding of them did not.
Recurrent FS down-regulated the expression of GABA(B)R subunits in a long term.
热性惊厥（FS）与γ-氨基丁酸（GABA）传递改变密切相关。GABA通过离子型受体（GABA(A)R和GABA(C)R）和代谢型受体（GABA(B)R）发挥作用。GABA(B)R位于突触前和突触后位点。刺激突触后受体可产生持久的抑制性突触后电位（IPSPs），这对抑制性神经传递的微调很重要，且由K(+)电导增加引起。在突触前位点，GABA(B)R通过抑制电压敏感性Ca(2+)通道介导对神经递质如GABA或谷氨酸释放的抑制。本研究旨在探讨反复热性惊厥后未成熟大鼠GABA(B)受体亚基的长期变化。
将大鼠随机分为对照组和热疗组。对照大鼠（n = 64）放入37℃水中5分钟。热疗组大鼠放入44.8℃水中5分钟。如果热疗组大鼠在5分钟内出现惊厥，惊厥一发生就将其从水中取出。进行10次水浸，每2天一次。研究出现10次惊厥的大鼠（FS(10)，n = 64）。暴露于热10次未出现惊厥的大鼠也作为单纯热疗组（H，n = 64）进行研究。在10次热疗的最后一次出现一次惊厥的大鼠作为单次惊厥组（FS(1)，n = 64）进行研究。其他大鼠用于其他研究。通过双荧光检测GABA(B)R(1)和GABA(B)R(2)共定位的变化；通过定量RT-PCR检测GABA(B)R(1)和GABA(B)R(2)的定量改变；通过免疫沉淀/蛋白质印迹检测GABA(B)R(2)与GABA(B)R(1)的结合。
FS(10)组最后一次热性惊厥后，GABA(B)R(1)、GABA(B)R(2)以及GABA(B)R(2)与GABA(B)R(1)的结合减少，后期GABA(B)R(1)的表达恢复正常，而GABA(B)R(2)及其结合未恢复。
反复FS长期下调GABA(B)R亚基的表达。
