myelin

myelin Myelin is the fatty insulating layer that surrounds many axons (nerve fibres) in both the central and peripheral nervous systems (CNS and PNS respectively). Nerve cells, with their axons, and glia are the two major cell types of the nervous systems. Myelin is formed from membranous sheets that are elaborated by glial cells: Schwann cells in the PNS and oligodendrocytes in the CNS. A major difference between these two is that Schwann cells each myelinate part of a single axon, whereas oligodendrocytes can myelinate as many as thirty axons in the CNS. Also, whereas Schwann cells are directly associated with their myelin sheath (Fig. 1), oligodendrocyte cell bodies connect by thin, tenuous processes to their multiple myelin sheets, each of which may be some distance from the cell body (Fig 3a).

Along the axons, myelin sheaths are arranged in segments that are separated by narrow regions of naked axolemma (the cell membrane of the axon) called nodes of Ranvier; these are the sites of action potential generation in myelinated axons (Fig. 1a and 3a). Nodes occur at regular intervals ranging from 0.3–2.0 mm, according to axon size. The myelin acts as a layer of high electrical resistance and low capacitance, facilitating the rapid saltatory (jumping) conduction of electrical impulses from node to node for long distances along axons that may be up to 1 m in length. Perhaps the most striking evidence of the importance of myelin comes from human demyelinating diseases such as multiple sclerosis, which specifically attacks oligodendrocytes. The subsequent loss of myelin causes the conduction block that underlies the crippling clinical symptoms of the disease.

Myelin is a complex structure that shows in cross-section as spirals around the axon to form a sheath made up of concentric layers (lamellae Fig.1b, 3b). The number of lamellae (N) determines the insulating properties of the sheath, whereas the intersegmental length (L) — the distance between nodes — determines the speed of conduction: since both N and L are directly and positively related to axon diameter, larger axons conduct faster than smaller ones. If unwrapped, a single myelin sheath would be seen to be a spade-like or trapezoid sheet of membrane, extraordinarily large relative to the axon it surrounded: in the order of 7 mm² (for a 15 μm diameter axon) or 0.4 mm² (for a 5 μm diameter axon); as though, say, a large handkerchief were wound around a length of thin string (Fig 3b). Thus, each myelinating cell maintains a myelin volume of 50 000–150 000 μm³ — according to axon diameter — an order of magnitude greater than its own volume. It is evident that the support of such a large volume of myelin places a considerable metabolic load on the myelinating cell, so, bearing in mind that each oligodendrocyte supports multiple sheaths, it is perhaps not surprising that oligodendrocytes have this exclusive function in the CNS. Moreover, myelin is continuously turned over and replaced by the myelinating cell.

It is difficult to imagine how the complex structure of myelin is formed. However, if the myelin sheet is envisaged as a flat layer of cytoplasm bounded by plasma membranes and then if the cytoplasm is extruded so that the two plasma membranes are directly opposed to one another, then this is essentially a single lamella of compacted myelin (Fig. 1b). Since each plasma membrane consists of a double phospholipid layer, the myelin sheet comprises two double fatty layers wrapped concentrically round the axon and it is these that give myelin its excellent insulatory properties. Antibodies to one of the lipids in myelin have been used to study oligodendrocytes.

In addition to the lipids, there are a number of proteins that are enriched in myelin and are specific to it. Some proteins are believed to be important in communication between the axon and the inner lamella of the myelin sheath; others fuse and stabilize the layers. Their importance is made clear when mutations of the genes that determine their formation cause loss of one or more of these proteins, resulting in the unravelling of myelin; demyelination; hypomyelination; loss of axonal function; and ensuing clinical symptoms, such as tremor and paraplegia.

Arthur M. Butt

Bibliography

Ransom, B. R. and Kettenham, H. (ed.) (1995). Neuroglia. Oxford University Press.

See also action potential; glia; nerves; white matter.