Wednesday, December 13, 2017

The role of the "myelin sheath" in conduction and multiple sclerosis

In April 2005 in an article in "Intellectual Property Today" entitled Intellectual Property at the Supreme Court and Before Congress [available LEXIS], LBE noted some "approximations" used by lawyers to explain certain science issues in the patent context, which explanations fundamentally were incorrect:

The situation here of an obvious falsity is distinct from one in which one errs for the sake of an approximation. For example, Michael Carlson, in "An Approach to Effective Opening Statements in Patent Cases," Int. Prop. Today, pp. 10-11 (Feb. 2005) analogized rf inductance heating in the semiconductor industry to heating in microwave ovens. Although microwave ovens are tuned to (approximately) excite a rotational resonance in water (ie, operate at about 2.45 GHz though the resonance is at about 10 GHz), they are not directly analogous to induction heating, which typically operates on an electronic conductor (e.g., graphite) in the frequency range 5 to 400 kHz and relies on eddy currents induced by ac magnetic fields. RF waves are not tuned to vibrate graphite "molecules." Similarly, close packing of spheres can produce ABAB. . . stacking (hexagonal closest packing) or ABCABC. . . (cubic closest packing), neither of which represent the tetrahedral arrangement of atoms in elemental silicon. Further, even optically isotropic liquids manifest some order, as can be perceived by x-ray diffraction, so they are not "amorphous" in terms of molecular order.

In certain meetings related to "multiple sclerosis," the bad effects arising from attack on the myelin sheath of CNS nerves is frequently analogized to the breaking down of the insulation of a common electrical cord.

For example, an overview at the national MS society webpage has the text:

Most of the axons in the central nervous system are wrapped in myelin, a substance rich in lipids (fatty substances) and proteins. Like the coating around an electrical wire, myelin insulates and protects the axon and helps speed nerve transmission.


The problematic part of this text is Like the coating around an electrical wire . Although myelin is an "insulator", the manner in which it functions is unlike the "coating" around a wire which conducts electricity via the movement of electrons.

from The Myelin Sheath by Pierre Morell and Richard H Quarles in Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. :

Myelin is an electrical insulator; however, its function of facilitating conduction in axons has no exact analogy in electrical circuitry. In unmyelinated fibers, impulse conduction is propagated by local circuits of ion current that flow into the active region of the axonal membrane, through the axon and out through adjacent sections of the membrane (Fig. 4-1). These local circuits depolarize the adjacent piece of membrane in a continuous, sequential fashion. In myelinated axons, the excitable axonal membrane is exposed to the extracellular space only at the nodes of Ranvier; this is the location of sodium channels [2]. When the membrane at the node is excited, the local circuit generated cannot flow through the high-resistance sheath and, therefore, flows out through and depolarizes the membrane at the next node, which might be 1 mm or farther away (Fig. 4-1). The low capacitance of the sheath means that little energy is required to depolarize the remaining membrane between the nodes, which results in local circuit spreading at an increased speed. Active excitation of the axonal membrane jumps from node to node; this form of impulse propagation is called saltatory conduction (Latin saltare, “to jump”). Such movement of the wave of depolarization is much more rapid than in unmyelinated fibers. Furthermore,because only the nodes of Ranvier are excited during conduction in myelinated fibers, Na+ flux into the nerve is much less than in unmyelinated fibers, where the entire membrane is involved. An example of the advantage of myelination is obtained by comparison of two different nerve fibers, both of which conduct at 25 m/sec at 20°C. The 500-mm diameter unmyelinated giant axon of the squid requires 5,000 times as much energy and occupies about 1,500 times as much space as the 12-mm diameter myelinated nerve in the frog.



A model of a simple insulated electrical cord does not manifest the function of the nodes of Ranvier in myelinated axons. Voltage-gated sodium channels (Nav) clustered at nodes of Ranvier promote rapid nerve conduction in the myelinated nerves of vertebrates. The nodes of Ranvier contain Na+/K+ ATPases, Na+/Ca2+ exchangers and a high density of voltage-gated Na+ channels, which allow the generation of the action potential.
The main reason for the increased conduction velocity [CV] of myelinated axons is that it reduces effective membrane capacitance.

One does note that Ranvier himself did bring up the analogy to electrical cables:

Ranvier extended the comparison to transatlantic cables: “Electrical wires immersed in a conductive medium need to be protected from this medium by a non-conductive sheath; it is on this principle that transatlantic cables are built.” (Ranvier, 1878).

from Zalc, Brain Research, Volume 1641, Part A, 15 June 2016, Pages 4-10.

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