IONIC CHANNELS IN MYELINATED NERVES

这项提案发起了一项重大的新倡议，旨在澄清 哺乳动物雪旺细胞中电压敏感离子通道的功能 有髓神经。原理是使用髓鞘基因的启动子来 选择性改变正常大鼠雪旺细胞离子通道的表达 神经测试关于雪旺细胞功能的特定假说 频道。 重点放在钾通道上。施万钾通道基因的研究进展 细胞的特征和它们的表达模式 髓鞘形成。然后，此表达模式将在 使用髓鞘基因启动子的转基因小鼠。转基因坐骨神经 随着雪旺细胞钾通道表达的改变， 检查是否有离子缓冲中断、髓鞘形成异常和改变 在轴突通道分布中。 次要强调的是钠离子通道。一种髓鞘基因启动子用于 将外源钠通道的表达导向雪旺细胞， 带有不同的药理‘标签’，以检验假设 雪旺细胞将钠通道转移到结节处的轴突细胞膜上 兰维尔的。 雪旺细胞离子体内功能分析的新方法 通道将普遍适用于其他部分的神经胶质细胞 大脑，并有可能发现离子通道之间的新联系 神经胶质细胞的失调与脱髓鞘的功能紊乱 疾病。

This proposal launches a major new initiative aimed at elucidating the function of voltage-sensitive ion channels in Schwann cells of mammalian myelinated nerves. The principle is to use promoters for myelin genes to alter selectively the expression of Schwann cell ion channels in intact nerves to test specific hypotheses about functions of Schwann cell channels. The emphasis is on potassium channels. Potassium channel genes in Schwann cells will be characterized and their expression pattern during myelination established. This expression pattern will then be altered in transgenic mice using myelin gene promoters. Transgenic sciatic nerves with an altered expression of potassium channel in Schwann cells will be examined for disrupted ionic buffering, abnormal myelination, and changes in axonal channel distribution. A minor emphasis is on sodium channels. A myelin-gene promoter is used to direct the expression of a foreign sodium channel to Schwann cells, which carries a distinct pharmacological 'tag', to test the hypothesis that Schwann cells transfer sodium channels to the axonal membrane at the node of Ranvier. This new approach for in vivo functional analysis of Schwann cell ion channels will be of general applicability to glial cells in other parts of the brain, and may potentially uncover novel linkages between ion channel dysregulation in glia and functional perturbation in demyelinating diseases.