CMT 1A: Channels, currents and mechanisms of accommodative processes in simulate

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Brain Res. 2007 Jul 20

Channels, currents and mechanisms of accommodative processes in

simulated cases of systematic demyelinating neuropathies.

Stephanova DI, Daskalova M, androv AS.

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

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

To clarify the mechanisms of accommodative processes in systematic

demyelinating neuropathies, this study presents the kinetics of the

ionic, transaxonal and transmyelin currents defining the

electrotonic potentials in different segments of human demyelinated

motor fibres.

The electrotonic potentials are obtained for fibres, which are in

simulated cases of internodal, paranodal and simultaneously of

paranodal internodal demyelinations, each of them systematic. The

computations used our previous double-cable model of the fibre.

The results show that the slow components of the electrotonic

potentials depend on the activation of the channel types in the

nodal or internodal axolemma, whereas the fast components of the

potentials are determined mainly by the passive cable responses,

i.e. by the capacitances and resistances of the corresponding

different segments along the fibre.

In the nodal segments, the depolarizing electrotonus is determined

mainly by the activation of the K(+) slow nodal channels, whereas in

the paranodal and internodal segments the potentials depend on the

activation of the K(+) fast and slow internodal channels. For the

hyperpolarizing electrotonus, the contribution of the activating

inward rectifier (IR) and leak (Lk) channels in the internodal

axolemma dominates in the total ionic currents.

The results show that the greater polarizing electrotonic potentials

and their defining currents in the mild systematic demyelinations

abnormally increase when these demyelinations are severe.

The study summarizes the insights gained from these modeling

investigations of the accommodative mechanisms underlying the

threshold electrotonus abnormalities observed in demyelinating

neuropathies such as Charcot-Marie-Tooth type 1A and chronic

inflammatory demyelinating polyneuropathy.