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

As nervous systems became increasingly complex and centralized, the need for efficient and rapid impulse conduction became pronounced. A solution to this problem, which independently appeared at least three times during evolution, was achieved by concentrating voltage-gated channels to unensheathed regions of the axon flanked by complex glial sheaths (Hildebrand et al. 1993). This collaboration between glial cells and axons achieves its apotheosis in the node of Ranvier. This exquisitely specialized structure, which is regularly spaced along the length of myelinated nerve fibers, enables saltatory conduction in which action potentials “jump” from node to node. In addition to increasing the speed of conduction, nodal conduction results in enormous economies of energy and space. For example, the unmyelinated squid giant axon occupies 15,000 times the space of a comparably conducting myelinated mammalian nerve and uses several thousandfold more energy. With these important advantages, however, also came new vulnerabilities, reflected in the large number of human diseases that affect the myelin sheath and/or the node.