Preferential conduction block of myelinated axons by nitric oxide

Conduction block by nitric oxide (NO) was examined in myelinated and unmyelinated axons from both the central nervous system and peripheral nervous system. In rat vagus nerves, mouse optic nerves at P12-P23, adult and developing mouse sciatic nerves, and mouse spinal cords, myelinated fibers were preferentially blocked reversibly by concentrations of NO similar to those encountered in inflammatory lesions. The possibility that these differences between myelinated and unmyelinated axons are due to the normal developmental substitution of Na⁺ channel subtype Na_v 1.6 for Na_v 1.2 at nodes of Ranvier was tested by repeating experiments on mice null for Na_v 1.6. Results were unchanged in this mutant. In shiverer optic nerve, which has only scattered regions with nodes of Ranvier, only the fastest component of the compound action potential was reduced. NO was compared with three other methods of blocking conduction: low Na⁺ , high K⁺ , and tetrodotoxin (TTX). In each of these three cases, unmyelinated axons lost conduction simultaneously with myelinated fibers. From changes in conduction velocity in myelinated axons as they were blocked, it was ascertained that NO acted most similarly to TTX. It was concluded that NO likely interacts with axonal Na⁺ channels through an intermediate that is associated with myelin. © 2016 Wiley Periodicals, Inc.