Glial cells and axo-glial interactions: implications for demyelinating disorders.

Two major glial cell types, the oligodendrocyte (which produces myelin) and the perinodal astrocyte (which contacts the sodium channel-rich axon membrane at the node of Ranvier), collaborate with the axon in forming the central myelinated fiber. Astrocytes have been demonstrated to synthesize voltage-sensitive sodium channels, and in some astrocytes these channels have neuronal properties. A variety of lines of evidence suggest that astrocytes play an important role in the reorganization of the axon membrane following demyelination. Possible functions of astrocytes include the targeting, or anchoring, of ion channels at specific sites within the axon membrane, or the specification of channel characteristics as a result of production of extracellular matrix molecules that interact with the glycosylated dome of sodium channels, or the synthesis of channels that are subsequently transferred to axons. It is also possible that astrocytes participate in ionic homeostasis at the node of Ranvier. A second major glial cell type, the oligodendrocyte, produces myelin during normal development. Morphologic studies have demonstrated that transplantation of myelin-forming cells, or their precursors, can result in the production of myelin with normal structure in the myelin-deprived CNS. In recent physiological studies, the function of axons following myelination by exogenous, transplanted glial cells has been examined. In regions of glial cell transplantation, there are significant increases in conduction velocities that approach normal values. Both of these lines of investigation, on astrocytes and myelin-forming oligodendrocytes/oligodendrocyte precursors, suggest that manipulation of glial cell properties may emerge as a viable strategy for promoting the recovery of conduction in CNS white matter axons following demyelination.