Differences between the channels, currents and mechanisms of conduction slowing/block and accommodative processes in simulated cases of focal demyelinating neuropathies

Abstract

To clarify the differences between the mechanisms of conduction slowing/block and accommodative processes in focal demyelinating neuropathies, this computational study presents the kinetics of the ionic, transaxonal and transmyelin currents defining the intracellular and electrotonic potentials in different segments of human motor nerve fibres. The computations use our previous double cable model of the fibres. The simulated fibres have focal demyelination of internodes, paranodes or both together. The intracellular potentials are defined mainly by the Na+ current, as the contribution of the K+ fast and K+ slow currents to the total nodal ionic current is negligible. The paranodal demyelinations cause an increase in the transaxonal current and a decrease in the transmyelin current at the paranodal segments. However, there is an inverse relationship between the transaxonal and transmyelin currents at the same segments in the cases of internodal demyelination. The internodal ionic channels beneath the myelin sheath do not contribute to the intracellular potentials, but they show a high sensitivity to long-lasting pulses. 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. However, the current kinetics changes (defining the investigated electrotonic changes) are relatively weak. The study summarizes the results from these modelling investigations on the mechanisms underlying the conduction slowing/block and accommodative processes in focal demyelinating neuropathies such as Guillain-Barré syndrome and multifocal motor neuropathy.

Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

“…The challenge lies in interpreting those observations. To this end, the group of Stephanova has simulated progressively greater degrees of systematic and focal demyelination of motor fibers to try to explain the observed physiological changes [ 26 , 27 , 28 , 29 , 30 , 31 ] (see Modeling section below).…”

Equivalent Circuit Implementation of Demyelinated Human Neuron in Spice

“…with an equivalent circuit model [24,26,31]. Some studies show that positive symptoms may also be present in Multiple Sclerosis due to either hyper excitability of injured axon, or persistent reflection of action potentials, which causes epileptic activity [36].…”

“…Nodes separated by resistors, however, do not account for a myelin sheath. The myelin sheath can be successfully modeled with a resistive and capacitive network known as internodes [31]. The nodes and internodes are separated by resistors on the inner and outer conductor, which represent length of the axon ( Figure 6).…”

“…Multiple sclerosis is the leading cause of disability for young adults, therefore studying its cure is of benefit [9,31]. Demyelination is caused by the immune system attacking the myelination surrounding the axon, which causes inflammation and leads to further auto immune attack [20].…”