Status epilepticus increases the intracellular accumulation of GABAA receptors
Status epilepticus increases the intracellular accumulation of GABAA receptors
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DOI：
10.1523/jneurosci.0900-05.2005
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发表时间：
2005-06-08
影响因子：
5.3
通讯作者：
Kapur, J
中科院分区：
文献类型：
--
作者：
Goodkin, HP;Yeh, JL;Kapur, J
癫痫持续状态是一种神经系统急症，可导致死亡和神经系统疾病。据推测，在癫痫持续状态期间抑制传递的减少是由于GABA(a)受体的快速修饰。然而，导致这种改变的机制尚未阐明。我们报道，使用结合电生理和细胞成像技术的体外癫痫持续状态模型，延长癫痫状破裂导致gaba介导的突触抑制减少。此外，我们发现GABA(A)受体的构成性内化是快速的，并且随着癫痫发作相关的神经元活动的增加而加速。神经元活动的抑制降低了内化的速度。这些发现表明，GABA(A)受体内化的速率受神经元活动的调节，其加速有助于减少长时间癫痫发作期间观察到的抑制性传递。
Status epilepticus is a neurological emergency that results in mortality and neurological morbidity. It has been postulated that the reduction of inhibitory transmission during status epilepticus results from a rapid modification of GABA(A) receptors. However, the mechanism(s) that contributes to this modification has not been elucidated. We report, using an in vitro model of status epilepticus combined with electrophysiological and cellular imaging techniques, that prolonged epileptiform bursting results in a reduction of GABA-mediated synaptic inhibition. Furthermore, we found that constitutive internalization of GABA(A) receptors is rapid and accelerated by the increased neuronal activity associated with seizures. Inhibition of neuronal activity reduced the rate of internalization. These findings suggest that the rate of GABA(A) receptor internalization is regulated by neuronal activity and its acceleration contributes to the reduction of inhibitory transmission observed during prolonged seizures.