Nedergaard M, Cooper A J, Goldman S A
Department of Anatomy and Cell Biology, New York Medical College, Valhalla 10595, USA.
J Neurobiol. 1995 Dec;28(4):433-44. doi: 10.1002/neu.480280404.
Spreading depression (SD) is a slowly propagating depression of cerebral neuronal activity and transmembrane ionic gradients, that arises in response to a variety of noxious stimuli. SD bears a strong resemblance to gap junction-mediated calcium waves among cultured astrocytes. Here, we show that gap junction-mediated intercellular diffusion is necessary for the generation of SD. Waves of SD in the isolated chicken retina were blocked by five different inhibitors of gap junctional coupling, which was assessed by the intercellular transit of Lucifer Yellow (LY). Each of these gap junction blockers inhibited both the migration of SD and the diffusion of LY in a dose-dependent manner. In contrast, glutamate-evoked calcium influx into retinal cells was not affected by these compounds. The results indicate that intercellular coupling through gap junctions is required for SD. Gap junction-mediated communication might therefore constitute an important mechanism in both normative and pathological brain function.
扩散性抑制（SD）是一种大脑神经元活动和跨膜离子梯度的缓慢传播性抑制，它是对多种有害刺激的反应而产生的。SD与培养的星形胶质细胞中缝隙连接介导的钙波极为相似。在此，我们表明缝隙连接介导的细胞间扩散对于SD的产生是必要的。分离的鸡视网膜中的SD波被五种不同的缝隙连接耦合抑制剂所阻断，缝隙连接耦合通过荧光黄（LY）的细胞间转运来评估。这些缝隙连接阻滞剂中的每一种都以剂量依赖性方式抑制了SD的迁移和LY的扩散。相比之下，谷氨酸诱发的钙流入视网膜细胞不受这些化合物的影响。结果表明，缝隙连接介导的细胞间耦合是SD所必需的。因此，缝隙连接介导的通讯可能在正常和病理脑功能中都构成一种重要机制。
