NMDA receptors regulate developmental gap junction uncoupling via CREB signaling
NMDA receptors regulate developmental gap junction uncoupling via CREB signaling
复制标题
DOI：
10.1038/nn1588
复制
发表时间：
2005-12-01
影响因子：
25
通讯作者：
Belousov, AB
中科院分区：
文献类型：
--
作者：
Arumugam, H;Liu, XH;Belousov, AB
通过间隙连接（电突触）的信号传导对于哺乳动物中枢神经系统的发育非常重要。在出生后发育过程中，神经元之间存在丰富的间隙连接耦合，随后减少并在成人中保持较低水平，仅限于特定的神经元亚群。在这里，我们报道了大鼠下丘脑体内和体外间隙连接的发育解偶联与连接蛋白 36 (Cx36) 蛋白表达的减少有关。 NMDA 谷氨酸受体、动作电位和钙-环 AMP 反应元件结合蛋白 (CREB) 的阻断可阻止发育间隙连接解偶联和 Cx36 下调，而 CREB 过表达会加速间隙连接解偶联和 Cx36 下调。发育间隙连接解偶联和 Cx36 下调不受非 NMDA 谷氨酸受体阻断的影响，并且不会发生在 NMDA 受体亚基 1 (NMDAR1) 敲除小鼠的下丘脑神经元中。这些结果表明，NMDA 受体活性通过 CREB 依赖性下调 Cx36 促进间隙连接的发育解偶联。
Signaling through gap junctions ( electrical synapses) is important in the development of the mammalian central nervous system. Abundant between neurons during postnatal development, gap junction coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. Here we report that developmental uncoupling of gap junctions in the rat hypothalamus in vivo and in vitro is associated with a decrease in connexin 36 (Cx36) protein expression. Both developmental gap junction uncoupling and Cx36 downregulation are prevented by the blockade of NMDA glutamate receptors, action potentials and the calcium - cyclic AMP response element binding protein ( CREB), and are accelerated by CREB overexpression. Developmental gap junction uncoupling and Cx36 downregulation are not affected by blockade of non-NMDA glutamate receptors, and do not occur in hypothalamic neurons from NMDA receptor subunit 1 (NMDAR1) knockout mice. These results demonstrate that NMDA receptor activity contributes to the developmental uncoupling of gap junctions via CREB-dependent downregulation of Cx36.