PDF(Pubmed)
Abstract：
KCNQs are voltage-gated K+ channels that control neuronal excitability and are mutated in epilepsy and autism spectrum disorder (ASD). KCNQs have been extensively studied in neurons, but their function in glia is unknown. Using voltage, calcium, and GABA imaging, optogenetics, and behavioral assays, we show here for the first time in Caenorhabditis elegans (C. elegans) that glial KCNQ channels control neuronal excitability by mediating GABA release from glia via regulation of the function of L-type voltage-gated Ca2+ channels. Further, we show that human KCNQ channels have the same role when expressed in nematode glia, underscoring conservation of function across species. Finally, we show that pathogenic loss-of-function and gain-of-function human KCNQ2 mutations alter glia-to-neuron GABA signaling in distinct ways and that the KCNQ channel opener retigabine exerts rescuing effects. This work identifies glial KCNQ channels as key regulators of neuronal excitability via control of GABA release from glia.
摘要：
KCNQ是控制神经元兴奋性的电压门控K通道，在癫痫和自闭症谱系障碍（ASD）中发生突变。KCNQ已经在神经元中进行了广泛的研究，但它们在胶质细胞中的作用是未知的.使用电压，钙，和GABA成像，光遗传学,和行为分析，我们在这里首次展示秀丽隐杆线虫(C.秀丽隐杆线虫），神经胶质KCNQ通道通过调节L型电压门控Ca2通道的功能来介导神经胶质的GABA释放，从而控制神经元的兴奋性。Further,我们表明，人类KCNQ通道在线虫神经胶质细胞中表达时具有相同的作用，强调跨物种的功能保护。最后,我们表明致病性功能丧失和功能获得人类KCNQ2突变以不同的方式改变神经胶质-神经元GABA信号传导,并且KCNQ通道开放剂瑞替加滨具有挽救作用.这项工作通过控制神经胶质中的GABA释放，将神经胶质KCNQ通道确定为神经元兴奋性的关键调节剂。
