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 Nav1.6 for Nav1.2 at nodes of Ranvier was tested by repeating experiments on mice null for Nav1.6. 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.
Department of Neuroscience, University of Rochester Medical Center, Rochester, New York.
Peter
P
Shrager
Department of Neuroscience, University of Rochester Medical Center, Rochester, New York.
Margaret
M
Youngman
D000818:Animals; D001340:Autonomic Nerve Block / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide
inflammation; ion channels; shiverer (RRID:IMSR_JAX:001428); unmyelinated