Chapter 4 Pathophysiology of demyelination and axonal degeneration

Publisher The physiological consequences of demyelination depend on the extent and severity of the demyelination as well as the types of nerve fibers involved. Demyelination impairs the transmission of impulses by changing the biophysical properties of the paranodal and internodal membranes and has been studied in single nerve fibers. For example, loss of the myelin sheath increases the capacitance and diminishes the transverse resistance in the paranodal and internodal regions. Demyelination in the paranodal region is especially critical for three reasons. First, retraction of the myelin sheath and Schwann cell processes increases the available nodal membrane area, thereby diluting the available depolarizing current over a larger membrane surface. Second, potassium channels that are normally present in the nearby paranodal–axolemmal membrane become exposed and as a result the membrane becomes hyperpolarized, thereby reducing the safety factor for transmission in the region. Third, the (sodium ion) Na+, (potassium ion) K+-ATPase electrogenic pump in the nodal region tends to drive the membrane toward the K+ equilibrium potential, further increasing the load on the internal longitudinal current (ILC) available for generating an action potential at the next nodal region in line.