Nerve Conduction Block by Nitric Oxide that is Mediated by the Axonal
Environment.
PETER SHRAGER, ANDREW W. CUSTER, KATIA KAZARINOVA, MATTHEW N. RASBAND AND
DAVID MATTSON.
Department of Neurobiology and Anatomy, Neuroscience Graduate Program,
Department of Biophysics, and Department of Neurology, University of Rochester
Medical Center, Rochester, NY 14642.
APStracts 4:280N, 1997.
ABSTRACT
Conduction in rat peripheral nerve has been monitored following the stimulated
release of nitric oxide from diethylamine-NONOate (DEA-NONOate). Branches of
the sciatic nerve were dissected, but left otherwise intact, and propagating
signals recorded externally. At levels consistent with inflammation, NO
exposure resulted in a complete loss of the compound action potential.
Conduction was fully restored on removal of the drug. Most notably, this loss
of excitability was dependent on the axonal environment. Removal of the
connective tissue sheaths surrounding the nerve bundle, a process that
normally enhances drug action, prevented block of signal propagation by nitric
oxide. The epineurium seemed not to be required, and the decreased
susceptibility to NO appeared to be correlated with a gradual loss of a
component of the endoneurium that surrounds individual fibers. Tested on the
rat vagus nerve, NO eliminated action potentials in both myelinated and
unmyelinated fibers. One chemical mechanism that is consistent with the
reversibility of block and the observed lack of effect of 8-Br-cGMP on
conduction is the formation of a nitrosothiol through reaction of NO with a
sulfhydryl group. In contrast to DEA-NONOate, S-nitrosocysteine, which can
both transfer NO+ to another thiol and also release nitric oxide, was
effective on both intact and desheathed preparations. It has previously been
demonstrated that chemical modification of invertebrate axons by sulfhydryl-
reactive compounds induces a slow inactivation of Na+ channels. Nitric oxide
block of axonal conduction may contribute to clinical deficits in inflammatory
diseases of the nervous system.
Received 29 April 1997; accepted in final form 25 September 1997.
APS Manuscript Number J339-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997