Clustering Sodium Channels at the Node of Ranvier: Close Encounters of the Axon–Glia Kind

cles, microtubules, and mitochondria, are also freAs nervous systems became increasingly complex and quently increased at the node, suggesting there is a centralized, the need for efficient and rapid impulse conbottleneck of axonal transport in both directions (Fabduction became pronounced. A solution to this problem, ricius et al., 1993) and local axonal–glial signaling. which independently appeared at least three times durFreeze fracture studies (Rosenbluth, 1976) have reing evolution, was achieved by concentrating voltagevealed that the nodal axolemma in both the CNS and gated channels to unensheathed regions of the axon PNS is enormously enriched in intramembranous partiflanked by complex glial sheaths (Hildebrand et al., 1993). cles (IMPs, .1200/mm) compared to the internode This collaboration between glial cells and axons achieves (,100/mm). These IMPs, which are associated with the its apotheosis in the node of Ranvier. This exquisitely outer leaflet (E face), are thought to correspond largely specialized structure, which is regularly spaced along to sodium channels that are concentrated in the node the length of myelinated nerve fibers, enables saltatory (see below). A dense undercoating of 25–35 nm is subjaconduction in which action potentials “jump” from node cent to, but slightly separated from, the axolemma. A to node. In addition to increasing the speed of conducsimilar undercoating is also present in the initial segment tion, nodal conduction results in enormous economies of the axon, the site of action potential initiation. of energy and space. For example, the unmyelinated There are some important differences in the structure squid giant axon occupies 15,000 times the space of a of the node in the CNS and PNS, reflecting their different comparably conducting myelinated mammalian nerve cellular constituents. In the PNS, hundreds of specialand uses several thousandfold more energy. With these ized microvilli project from the outer collar of adjacent