Shrager P, Rubinstein C T
Department of Physiology, University of Rochester Medical Center, New York 14642.
J Gen Physiol. 1990 May;95(5):867-89. doi: 10.1085/jgp.95.5.867.
Demyelination was initiated in Xenopus sciatic nerves by an intraneural injection of lysolecithin over a 2-3-mm region. During the next week macrophages and Schwann cells removed all remaining damaged myelin by phagocytosis. Proliferating Schwann cells then began to remyelinate the axons, with the first few lamellae appearing 13 d after surgery. Action potentials were recorded optically through the use of a potential-sensitive dye. Signals could be detected both at normal nodes of Ranvier and within demyelinated segments. Before remyelination, conduction through the lesion occurred in only a small fraction of the fibers. However, in these particular cases we could demonstrate continuous (nonsaltatory) conduction at very low velocities over long (greater than one internode) lengths of demyelinated axons. We have previously found through loose patch clamp experiments that the internodal axolemma contains voltage-dependent Na+ channels at a density approximately 4% of that at the nodes. These channels alone, however, are insufficient for successful conduction past the transition point between myelinated and demyelinated regions. Small improvements in the passive cable properties of the axon, adequate for propagation at this site, can be realized through the close apposition of macrophages and Schwann cells. As the initial lamellae of myelin appear, the probability of success at the transition zone increases rapidly, though the conduction velocity through the demyelinated segment is not appreciably changed. A detailed computational model is used to test the relative roles of the internodal Na+ channels and the new extracellular layer. The results suggest a possible mechanism that may contribute to the spontaneous recovery of function often seen in demyelinating disease.
通过在非洲爪蟾坐骨神经内 2 - 3 毫米区域注射溶血卵磷脂引发脱髓鞘。在接下来的一周内，巨噬细胞和施万细胞通过吞噬作用清除所有剩余的受损髓鞘。然后增殖的施万细胞开始对轴突进行重新髓鞘化，术后 13 天出现最初的几层髓鞘板。通过使用电位敏感染料以光学方式记录动作电位。在正常的郎飞结和脱髓鞘节段内都能检测到信号。在重新髓鞘化之前，只有一小部分纤维能够通过损伤部位传导。然而，在这些特定情况下，我们能够证明在脱髓鞘轴突的很长（大于一个节间）长度上以非常低的速度进行连续（非跳跃式）传导。我们之前通过松散膜片钳实验发现，节间轴膜上电压依赖性 Na⁺通道的密度约为节点处的 4%。然而，仅这些通道不足以成功传导通过髓鞘化和脱髓鞘区域之间的过渡点。通过巨噬细胞和施万细胞的紧密贴附，可以实现轴突被动电缆特性的微小改善，足以在此部位进行传播。随着髓鞘最初的几层髓鞘板出现，过渡区成功传导的概率迅速增加，尽管通过脱髓鞘节段的传导速度没有明显变化。使用详细的计算模型来测试节间 Na⁺通道和新的细胞外层的相对作用。结果提示了一种可能的机制，这可能有助于解释脱髓鞘疾病中常见的功能自发恢复现象。
