Membrane property abnormalities in simulated cases of mild systematic and severe

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Eur Biophys J. 2007 Sep 5

Membrane property abnormalities in simulated cases of mild

systematic and severe focal demyelinating neuropathies.

Stephanova D, Daskalova M.

Institute of Biophysics, Bulgarian Academy of Sciences, Acad. G.

Bontchev Str., Bl. 21, Sofia, 1113, Bulgaria

The investigation of multiple nerve membrane properties by

mathematical models has become a new tool to study peripheral

neuropathies. In demyelinating neuropathies, the membrane properties

such as potentials (intracellular, extracellular, electrotonic) and

indices of axonal excitability (strength-duration time constants,

rheobases and recovery cycles) can now be measured at the peripheral

nerves.

This study provides numerical simulations of the membrane properties

of human motor nerve fibre in cases of internodal, paranodal and

simultaneously of paranodal internodal demyelinations, each of them

mild systematic or severe focal. The computations use our previous

multi-layered model of the fibre. The results show that the

abnormally greater increase of the hyperpolarizing electrotonus,

shorter strength-duration time constants and greater axonal

superexcitability in the recovery cycles are the characteristic

features of the mildly systematically demyelinated cases.

The small decrease of the polarizing electrotonic responses in the

demyelinated zone in turn leads to a compensatory small increase of

these responses outside the demyelinated zone of all severely

focally demyelinated cases.

The paper summarizes the insights gained from these modeling studies

on the membrane property abnormalities underlying the variation in

clinical symptoms of demyelination in Charcot-Marie-Tooth disease

type 1A, chronic inflammatory demyelinating polyneuropathy, Guillain-

Barré syndrome and multifocal motor neuropathy.

The model used provides an objective study of the mechanisms of

these diseases which up till now have not been sufficiently well

understood, because quite different assumptions have been given in

the literature for the interpretation of the membrane property

abnormalities obtained in hereditary, chronic and acquired

demyelinating neuropathies.