Schafer Dorothy P, Custer Andrew W, Shrager Peter, Rasband Matthew N
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Neuron Glia Biol. 2006 May;2(2):69-79. doi: 10.1017/S1740925X06000093.
Action potential conduction velocity increases dramatically during early development as axons become myelinated. Integral to this process is the clustering of voltage-gated Na(+) (Nav) channels at regularly spaced gaps in the myelin sheath called nodes of Ranvier. We show here that some aspects of peripheral node of Ranvier formation are distinct from node formation in the CNS. For example, at CNS nodes, Nav1.2 channels are detected first, but are then replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels are detected at newly forming nodes. By contrast, the earliest Nav-channel clusters detected during developmental myelination in the PNS have Nav1.6. Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we show that accumulation of the cell adhesion molecule neurofascin always precedes Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186) accumulates first, but occasionally paranodal neurofascin is detected first. We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS.
在早期发育过程中，随着轴突形成髓鞘，动作电位传导速度显著增加。这一过程的一个重要部分是电压门控钠（Na⁺）通道（Nav）在髓鞘中规则间隔的间隙（称为郎飞结）处聚集。我们在此表明，周围神经系统郎飞结形成的某些方面与中枢神经系统中的节点形成不同。例如，在中枢神经系统的节点处，首先检测到Nav1.2通道，但随后被Nav1.6取代。同样，在中枢神经系统的髓鞘再生过程中，在新形成的节点处检测到Nav1.2通道。相比之下，在周围神经系统发育性髓鞘形成过程中最早检测到的Nav通道簇具有Nav1.6。此外，在周围神经系统的髓鞘再生过程中，在新节点处检测到Nav1.6。最后，我们表明细胞粘附分子神经束蛋白的积累总是先于周围神经系统中Nav通道的聚集。在大多数情况下，轴突神经束蛋白（NF-186）首先积累，但偶尔也会首先检测到节旁神经束蛋白。我们认为导致Nav通道聚集的事件存在异质性，这表明多种机制可能有助于周围神经系统中郎飞结的形成。
