IONIC CHANNELS IN MAMMALIAN MYELINATED NERVOUS SYSTEM

这项提议的长期目标是阐明 神经功能的哺乳动物有髓纤维在两个正常 生理条件和正常雪旺氏细胞 细胞-轴突关系受到干扰。 不同类型的 电生理技术将用于测量各种特定的 单个哺乳动物有髓轴突和雪旺细胞的膜特性 它们之间的关系被实验性地扰乱了。 电压钳实验将在单个哺乳动物的有髓鞘细胞上进行。 纤维 哺乳动物体内离子通道沿着的互补分布 有髓鞘轴突，Na通道聚集在节点，K通道 位于副阳极，将进行检查。 扰动的影响 我们将探讨许旺细胞-轴突在此通道分布上的关系。 此外，通常隐藏在下面的结间钾通道的作用 将检查髓磷脂。 特别是，假设这些 结间钾通道在支持静息 将测试节点的潜力。 通常将Na通道聚集在Ranvier节点的机制将 检查和正常的雪旺细胞轴突关系的要求， 将探讨这种分组。 相关地，Na的横向扩散 将测量从节点到节间的通道， 计算哺乳动物纤维中Na通道的横向扩散。 该提案的一个独特之处是采用了新的和 单根有髓纤维的膜片钳技术。 高分辨率 在脱髓鞘中离子通道的空间分布的绘图可以 实现。 具体而言，动力学性质和空间 慢性淋巴结炎后出现的新结间钠通道密度 将检查脱髓鞘。 通道上的此类测量 再分布将与功能恢复相关。 最后，对哺乳动物细胞膜兴奋特性的表达进行了研究。 将用膜片钳技术探索雪旺细胞。 具体来说，发育和轴突接触对神经元生长的影响， 将检测Na和K通道在哺乳动物许旺细胞上的表达。

The long-term objective of this proposal is to elucidate the physiology of nerve functions in mammalian myelinated fibers under both normal physiological conditions and conditions in which the normal Schwann cell-axon relation has been disturbed. Different types of electrophysiological techniques will be used to measure various specific membrane properties on single mammalian myelinated axons and Schwann cells in which the relations between them have been experimentally disturbed. Voltage clamp experiments will be performed on single mammalian myelinated fibers. The complementary distribution of ionic channels along a mammalian myelinated axon, with Na channels clustered at the node and K channels located in the paranode, will be examined. The effect of perturbing the Schwann cell-axon relation on this channel distribution will be explored. Furthermore, the role of the internodal K channels that normally hide under the myelin will be examined. In particular, the hypothesis that these internodal K channels play a crucial role in supporting the resting potential of a node will be tested. The mechanisms that normally cluster Na channels at a node of Ranvier will be examined and the requirement of a normal Schwann cell-axon relation for such a clustering will be explored. Relatedly, the lateral diffusion of Na channels from a node to an internode will be measured and the coefficient of lateral diffusion of Na channels in a mammalian fiber will be calculated. A unique feature of this proposal is the application of the new and powerful patch clamp to single myelinated fibers. A high resolution mapping of the spatial distribution of ionic channels in demyelination can be achieved. Specifically, the kinetic properties and the spatial densities of the new internodal Na channels that appear after chronic demyelination will be examined. Such measurements on channel redistribution will then be correlated with functional recovery. Finally, the expression of excitable membrane properties on mammalian Schwann cells will be explored with the patch clamp technique. Specifically, the influence of development and axon contact on the expression of Na and K channels on mammalian Schwann cells will be examined.