Toronto Western Research Institute, Epilepsy Program, University Health Network, Toronto, Ontario, Canada M5T2S8.
Brain Res. 2012 Dec 3;1487:54-60. doi: 10.1016/j.brainres.2012.06.059. Epub 2012 Jul 11.
Glia play an under-recognized role in epilepsy. This review examines the involvement of glial connexins (Cxs) and pannexins (Panxs), proteins which form gap junctions and membrane hemichannels (connexins) and hemichannels (pannexins), in epilepsy. These proteins, particularly glial Cx43, have been shown to be upregulated in epileptic brain tissue. In a cobalt model of in vitro seizures, seizures increased Panxs1 and 2 and Cx43 expression, and remarkably reorganized the interrelationships between their mRNA levels (transcriptome) which then became statistically significant. Gap junctions are highly implicated in synchronous seizure activity. Blocking gap junctional communication (GJC) is often anticonvulsant, and assumed to be due to blocking gap junctionally-medicated electrotonic coupling between neurons. However, in organotypic hippocampal slice cultures, connexin43 specific peptides, which attenuate GJC possibly by blocking connexon docking, diminished spontaneous seizures. Glia have many functions including extracellular potassium redistribution, in part via gap junctions, which if blocked, can be seizuregenic. Glial gap junctions are critical for the delivery of nutrients to neurons, which if interrupted, can depress seizure activity. Other functions of glia possibly related to epileptogenesis are mentioned including anatomic reorganization in chronic seizure models greatly increasing the overlapping domains of glial processes, changes in neurotransmitter re-uptake, and possible glial generation of currents and fields during seizure activity. Finally there is recent evidence for Cx43 hemichannels and Panx1 channels in glial membranes which could play a role in brain damage and seizure activity. Although glial Cxs and Panxs are increasingly recognized as contributing to fundamental mechanisms of epilepsy, the data are often contradictory and controversial, requiring much more research. This article is part of a Special Issue entitled Electrical Synapses.
神经胶质在癫痫中起着被低估的作用。这篇综述检查了神经胶质连接蛋白（Cxs）和连接蛋白（Panxs）的参与，这些蛋白质形成间隙连接和膜半通道（连接蛋白）和半通道（连接蛋白），在癫痫中。这些蛋白质，特别是神经胶质 Cx43，已被证明在癫痫脑组织中上调。在体外癫痫发作的钴模型中，癫痫发作增加了 Panxs1 和 2 和 Cx43 的表达，并显著重新组织了它们的 mRNA 水平（转录组）之间的相互关系，然后变得具有统计学意义。间隙连接在同步癫痫活动中高度涉及。阻断间隙连接通讯（GJC）通常是抗惊厥的，并且假定是由于阻断神经元之间的间隙连接介导的电偶联。然而，在器官型海马切片培养物中，连接蛋白 43 特异性肽，通过阻断连接子对接来减弱 GJC，减少自发性癫痫发作。神经胶质具有许多功能，包括通过间隙连接部分重新分布细胞外钾，这如果被阻断，可能会导致癫痫发作。神经胶质间隙连接对于向神经元输送营养物质至关重要，如果中断，可能会抑制癫痫发作。神经胶质的其他功能可能与癫痫发生有关，包括在慢性癫痫模型中解剖结构的重新组织大大增加了神经胶质过程的重叠域，神经递质再摄取的变化，以及在癫痫发作期间神经胶质产生电流和场的可能性。最后，有最近的证据表明，神经胶质膜中的 Cx43 半通道和 Panx1 通道可能在脑损伤和癫痫发作中发挥作用。尽管神经胶质 Cxs 和 Panxs 越来越被认为是癫痫基本机制的贡献者，但数据往往相互矛盾和有争议，需要更多的研究。本文是题为“电突触”的特刊的一部分。
