Caddick S J, Hosford D A
Division of Neurology, Duke University Medical Center, Durham, NC, USA.
Mol Neurobiol. 1996 Aug;13(1):23-32. doi: 10.1007/BF02740750.
Generalized absence seizures in humans are a unique type of epilepsy characterized by a synchronous, bilateral 3-Hz spike and wave discharge emanating from a cortical and thalamic network within the brain. The availability of a number of pharmacological and genetic animal models has provided us with the means with which to investigate the cellular and molecular mechanisms underlying these seizures. Over the last few years a significant amount of research in these models has focused on the role of the inhibitory GABAB receptors, which have been previously described in a number of brain areas as being responsible for a long-lasting hyperpolarization and depression in neurotransmitter release. Initial studies provided evidence that the GABAB receptor was capable of generating the low threshold calcium spike required for initiation of the burst firing, leading researchers to hypothesize that the GABAB receptors played a significant role in these seizures. Subsequent research took advantage of the new generation of GABAB antagonists that became available in the early 1990s and demonstrated that in a number of models the seizures could be abolished by the administration of one of these compounds. Further biochemical, molecular, and electrophysiological experiments have been carried out to determine the exact involvement of GABAB receptors and their mechanism of action. The current evidence and interpretations of this work are presented here.
人类的全身性失神发作是一种独特的癫痫类型，其特征是大脑内由皮质和丘脑网络产生的同步双侧3赫兹棘波和慢波放电。多种药理学和基因动物模型的出现为我们研究这些发作背后的细胞和分子机制提供了手段。在过去几年中，针对这些模型的大量研究集中在抑制性GABAB受体的作用上，此前在多个脑区中已描述该受体负责神经递质释放的持久超极化和抑制。初步研究提供的证据表明，GABAB受体能够产生引发爆发性放电所需的低阈值钙尖峰，这使研究人员推测GABAB受体在这些发作中起重要作用。随后的研究利用了20世纪90年代初可用的新一代GABAB拮抗剂，并证明在多种模型中，给予其中一种化合物可消除发作。已经进行了进一步的生化、分子和电生理实验，以确定GABAB受体的确切参与情况及其作用机制。本文介绍了这项工作的当前证据和解释。
