3.3 Demyelinating diseases with an emphasis on Multiple Sclerosis
3.3 Demyelinating diseases with an emphasis on Multiple Sclerosis
Myelin is produced from the cell membranes of either Schwann cells (for neurons in the PNS) or oligodendroglia/oligodendrocytes (for neurons in the CNS). As such, myelin is enriched with membrane lipids and proteins that are found within these cells. Normally myelin functions to increase nerve cell conduction by increasing the biophysical property of the membrane resistance (i.e. a neuron cell membrane’s leakiness). Myelin reduces membrane leakiness by preventing open channels and as a result, increasing how far a single electrical impulse within the axon will travel. Importantly this also increases how quickly an action potential will travel down an axon – myelin greatly increases the conduction velocity of a neuron (Figure 1.).
Myelin helps neurons to cheat
Various factors help to determine how fast an action potential travels down an axon (called the conduction velocity). The biophysical features of a neuron including axonal diameter and membrane leakiness, help scientists to determine what is known as the length or space constant (lambda or λ) for each neuron. Why is this λ value important? λ is directly proportional to the conduction velocity – so the factors that determine λ also determine a neuron’s conduction velocity. Let’s not forget –speed thrills within the CNS and brain, and the faster a signal gets there, the more the brain likes it.
Another reason for myelination includes having a lot of neurons so space is a premium. Although the length constant is inversely related to the axonal diameter (i.e. bigger diameter axons have bigger length constants), we need to pack as many neurons into a small space as possible. So within the brain, faster communication means myelination is key.
Large vertebrate nerve fibres are wrapped in myelin sheaths formed by central oligodendroglial cells or Schwann cells in the periphery but the myelin only wraps the axon at specific locations. Myelin is interrupted at regularly spaced intervals or nodes. This helps the neuron because during action potential propagation the excitatory signal jumps from one node to the next, and we call this saltatory conduction which is much faster than passive electronic spread. In addition, myelin also helps Rm (leakiness or membrane resistance) because it only directs voltage-sensitive Na+ channels to highly concentrated areas known as the nodes of Ranvier (Figure 2.). So in many ways, myelin helps the neuron “cheat’ by limiting leakiness (i.e. open channels to specific areas). As shown in Figure 2., Before glial ensheathment, sodium channels are distributed uniformly, and at low density. At the time of glial ensheathment but before the formation of compact myelin, loose clusters of sodium channels develop at sites that will eventually become nodes. Following the formation of compact myelin and mature paranodal axon-glial cell junctions, well-defined nodal clusters of voltage-gated sodium channels are establi