Mathews G C, Bolos-Sy A M, Holland K D, Isenberg K E, Covey D F, Ferrendelli J A, Rothman S M
Medical Scientist Training Program, St. Louis Children's Hospital, Missouri 63110.
Neuron. 1994 Jul;13(1):149-58. doi: 10.1016/0896-6273(94)90465-0.
Although we now have extensive knowledge about the GABAA receptor subunits determining benzodiazepine modulation of channel function, little is known about subunits influencing other modulatory sites on the GABAA receptor-chloride channel complex. We have identified a developmental change in subunit composition of the GABAA receptor in cultured cerebellar granule neurons that eliminates benzodiazepine-mediated enhancement of GABA responses and alters modulation by a substituted gamma-butyrolactone. Based on data from sequential PCR experiments, we mimicked the functional properties of early and mature receptors with heterologous expression of specific subunit combinations. This report describes one of the most extensive cell- and site-specific developmental changes for an ion channel seen to date.
尽管我们现在对决定苯二氮䓬调节通道功能的GABAA受体亚基已有广泛了解，但对于影响GABAA受体-氯离子通道复合物上其他调节位点的亚基却知之甚少。我们已经确定了培养的小脑颗粒神经元中GABAA受体亚基组成的发育变化，这种变化消除了苯二氮䓬介导的GABA反应增强，并改变了一种取代γ-丁内酯的调节作用。基于序列PCR实验的数据，我们通过特定亚基组合的异源表达模拟了早期和成熟受体的功能特性。本报告描述了迄今为止所观察到的离子通道最广泛的细胞和位点特异性发育变化之一。
