Channels, currents and mechanisms of accommodative processes in simulated cases of systematic demyelinating neuropathies.
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.
Stephanova
Diana I
DI
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria. dsteph@shiva.bio.bas.bg
Daskalova
Mariya
M
Alexandrov
Alexandar S
AS
D000220:Adaptation, Biological / Q000502:physiology*; D020274:Autoimmune Diseases of the Nervous System / Q000473:pathology* / Q000503:physiopathology*; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009431:Neural Conduction / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D011930:Reaction Time / Q000502:physiology; D012720:Severity of Illness Index
D007473:Ion Channels