Nerve conduction block by nitric oxide that is mediated by the axonal environment

Peter Shrager, Andrew W. Custer, Katia Kazarinova, Matthew N. Rasband, David Mattson

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61 Scopus citations


Conduction in rat peripheral nerve has been monitored following the stimulated release of nitric oxide (NO) 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 drag. 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 nitrosonium cation (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.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalJournal of Neurophysiology
Issue number2
StatePublished - Feb 1998

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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