Impulse conduction in inhomogeneous axons: effects of variation in voltage-sensitive ionic conductances on invasion of demyelinated axon segments and preterminal fibers.

Conduction in inhomogeneous axons may be blocked by several mechanisms. Conduction in demyelinated axons may fail since normal internodal membrane is inexcitable, because values of sodium conductance are too low to support impulse conduction. In addition, focal loss of myelin causes increased current leakage which slows or blocks invasion of impulses into the demyelinated zone due to inadequate current density. Similar considerations apply to the invasion of non-myelinated preterminal axons from myelinated parent fibers, where conduction can be blocked as a result of inadequate current density. A cable model of an axon is presented which allows myelinated regions, regions without myelin, and variable length transition zones of redistributed channel densities, to be studied. Action potentials and membrane currents were studied. Computer simulations using this model show that the safety factor for invasion is dependent on temperature. These studies also show that small changes in axon membrane properties, at the transition region between the myelinated zone and the region without myelin, may promote invasion of the region without myelin. In particular, increasing sodium conductance (gNa) or decreasing potassium conductance (gK) promotes invasion. Because of the non-linear behavior of excitable membranes the spatial distribution of channels is shown also to have significant effects on invasion. Thus, relatively small degrees of membrane reorganization may lead to functional changes with respect to the invasion of demyelinated axon regions. Similarly, the properties of the heminode at the distal part of the parent myelinated fiber may determine the invasion characteristics of non-myelinated terminal axons.