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Remyelination of dorsal column axons by endogenous Schwann cells restores the normal pattern of Nav1.6 and Kv1.2 at nodes of Ranvier.

Abstract

Demyelination of CNS axons occurs in a number of pathological conditions, including multiple sclerosis and contusion-type spinal cord injury. The demyelination can be repaired by remyelination in both humans and rodents, and even within the CNS remyelination can be achieved by endogenous and/or exogenous Schwann cells, the myelinating cells of the PNS. Remyelinated axons can often conduct impulses securely, but the organization of ion channels at long-term remyelinated nodes is not known. In the present study, the expression of voltage-gated sodium (Na(v)) and potassium (K(v)) channels along central axons remyelinated by endogenous Schwann cells has been studied in lesions induced more than 1 year previously by the intraspinal injection of ethidium bromide (EB). The expression of the channels at long-term nodes formed by Schwann cell remyelination has been compared with that present in nascent nodes formed in the adult at 18 and 23 days post-EB injection. Immunohistochemical studies revealed that long-term nodes formed by Schwann cell remyelination exhibit a clustering of Na(v)1.6 sodium channels within the nodal membrane, with the Shaker-type potassium channel K(v)1.2 segregated within the juxtaparanodal region, similar to the arrangement at normal mature CNS nodes. Na(v)1.2 was not detected at nodes formed by Schwann cells at any stage of their development. Moreover, Na(v)1.6, but not Na(v)1.2, was clustered at nascent nodes formed by remyelinating Schwann cells 18 and 23 days following EB injection. These observations show that endogenous Schwann cells can establish and maintain nodes of Ranvier on central axons for over one year, and that the nodes exhibit an apparently normal distribution of sodium and potassium channels, with Na(v)1.6 the predominant subtype of sodium channel present at such nodes at all stages of their development.

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