IONIC CHANNELS IN MAMMALIAN MYELINATED NERVOUS SYSTEM

这项建议的长期目标是阐明心脏的生理学。 哺乳动物有髓纤维在两种正常状态下的神经功能 生理条件和正常的施万氏 细胞-轴突关系受到干扰。不同类型的 电生理技术将被用来测量各种特定的 单个哺乳动物有髓轴突和雪旺细胞的膜特性 它们之间的关系受到了实验上的干扰。 电压钳实验将在单个有髓哺乳动物身上进行 纤维。哺乳动物体内离子通道的互补分布 有髓轴突，Na通道聚集在结节，K通道聚集 位于副阳极处，将被检查。扰乱世界的影响 我们将探讨雪旺细胞-轴突在这一通道分布上的关系。 此外，正常情况下隐藏在下层的节间K通道的作用 将对髓鞘进行检查。尤其是，这些假设 结间K通道在支持静息过程中起着至关重要的作用 将测试节点的潜力。 通常在Ranvier节点处聚集Na通道的机制将 和正常雪旺细胞-轴突关系的要求 这样的集群将被探索。与之相关的是，Na的横向扩散 将测量从节点到节点间的通道，并且系数 将计算哺乳动物纤维中钠通道的横向扩散。 这项提议的一个独特之处是应用了新的和 强大的膜片钳对单个有髓纤维。高分辨率 脱髓鞘罐头中离子通道空间分布的定位 才能实现。具体地说，动力学性质和空间 慢性心力衰竭后出现的新的结间钠通道密度 将对脱髓鞘进行检查。在航道上进行这种测量 然后，再分配将与功能恢复相关。 最后，兴奋性膜特性在哺乳动物身上的表达 雪旺细胞将用膜片钳技术进行探索。 具体地说，发育和轴突接触对 将检测哺乳动物雪旺细胞上Na和K通道的表达。

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.