The effects of paranodal myelin damage on action potential depend on axonal structure.

Biophysical computational models of axons provide an important tool for quantifying the effects of injury and disease on signal conduction characteristics. Several studies have used generic models to study the average behavior of healthy and injured axons; however, few studies have included the effects of normal structural variation on the simulated axon's response to injury. The effects of variations in physiological characteristics on axonal function were mapped by altering the structure of the nodal, paranodal, and juxtaparanodal regions across reported values in three different caliber axons (1, 2, and 5.7 μm). Myelin detachment and retraction were simulated to quantify the effects of each injury mechanism on signal conduction. Conduction velocity was most affected by axonal fiber diameter (89%), while membrane potential amplitude was most affected by nodal length (86%) in healthy axons. Postinjury axonal functionality was most affected by myelin detachment in the paranodal and juxtaparanodal regions when retraction and detachment were modeled simultaneously. The efficacy of simulated potassium channel blockers on restoring membrane potential and velocity varied with axonal caliber and injury type. The structural characteristics of axons affect their functional response to myelin retraction and detachment and their subsequent response to potassium channel blocker treatment.