CMT 1A: The aqueous layers within the myelin sheath modulate the membrane prop

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J Integr Neurosci. 2011 Mar;10(1):89-103.

The aqueous layers within the myelin sheath modulate the membrane properties of

simulated hereditary demyelinating neuropathies.

Stephanova DI, Krustev SM, Daskalova M.

Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of

Sciences, Acad. G. Bontchev Str. Bl. 21, Sofia 1113, Bulgaria.

Abstract

To expand our studies on the mechanisms underlying the clinical decline of the

nerve excitability properties in patients with hereditary demyelinating

neuropathies, the contribution of myelin sheath aqueous layers on multiple

membrane properties of simulated fiber demyelinations is investigated.

Three progressively greater degrees of internodal systematic demyelinations (two

mild and one severe termed as ISD1, ISD2 and ISD3, respectively) without/with

aqueous layers are simulated using our previous multi-layered model of human

motor nerve fiber.

The calculated multiple membrane excitability properties are as follows:

potentials (intracellular action, electrotonic), strength-duration time

constants, rheobasic currents and recovery cycles. They reflect the propagating,

accommodative and adaptive processes in the fibers.

The results show that all membrane properties, except for the strength-duration

time constants and refractoriness, worsen when the myelin lamellae and their

corresponding aqueous layers are uniformly reduced along the fiber length.

The effect of the aqueous layers is significantly higher on the accommodative

and adaptive processes than on the propagating processes in the fibers. Our

multi-layered model better approximated some of the functional deficits

documented for axons of patients with Charcot-Marie-Tooth disease type 1A.

The study provides new and important information on the mechanisms underlying

the pathophysiology of hereditary demyelinating neuropathies.