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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Abnormal GABA_A receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes
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Abnormal GABA_A receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes

机译：人类癫痫海马下皮层微移植到非洲爪蟾卵母细胞的GABA_A受体异常

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摘要

We studied the properties of GABA_A receptors microtransplanted from the human temporal lobe epilepsy (TLE)-associated brain regions to Xenopus oocytes. Cell membranes, isolated from surgically resected brain specimens of drug-resistant TLE patients, were injected into frog oocytes, which rapidly incorporated human GABA_a receptors, and any associated proteins, into their surface membrane. The receptors originating from different epileptic brain regions had a similar run-down but an affinity for GABA that was ≈60℅ lower for the subiculum receptors than for receptors issuing from the hippocampus proper or the temporal lobe neocortex. Moreover, GABA currents recorded in oocytes injected with membranes from the subiculum had a more depolarized reversal potential compared with the hippocampus proper or neocortex of the same patients. Quantitative RT-PCR analysis was performed of the GABA_a receptor α1- to α5-, β1- to β3-, γ2- to γ3-, and δ-subunit mRNAs. The levels of expression of the α3-, α5-, and β1- to β3-subunit mRNAs are significantly higher, with the exception of γ2- subunit whose expression is lower, in subiculum compared with neocortex specimens. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE subiculum leads to the expression of GABA_a receptors with a relatively low affinity. This abnormal behavior of the subiculum GABA_A receptors may contribute to epileptogenesis.
机译：我们研究了从人类颞叶癫痫（TLE）相关的大脑区域微移植到非洲爪蟾卵母细胞的GABA_A受体的特性。从耐药的TLE患者的手术切除的脑标本中分离出的细胞膜被注入到青蛙卵母细胞中，该卵母细胞将人GABA_a受体和任何相关蛋白迅速整合到其表面膜中。来自不同癫痫脑区的受体具有类似的衰变，但对GABA的亲和力对下丘脑受体比从海马固有或颞叶新皮层发出的受体低约60℅。此外，与相同患者的海马固有层或新皮层相比，在注射有来自下丘脑膜的卵母细胞中记录的GABA电流具有更大的去极化逆转潜力。对GABA_a受体α1-至α5-，β1-至β3-，γ2-至γ3-和δ亚基mRNA进行了定量RT-PCR分析。与新皮层标本相比，亚皮层亚基中α3-，α5-和β1-至β3-亚基的mRNA的表达水平明显较高，但γ2-亚基的表达水平较低。我们的结果表明，TLE亚细小体中GABA受体亚基的异常转录导致GABA_a受体的表达具有相对较低的亲和力。下颌GABA_A受体的这种异常行为可能有助于癫痫发生。

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