The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 529-536
Copyright ©1998 The American Physiological Society

Nerve Conduction Block by Nitric Oxide That Is Mediated by the Axonal Environment

Peter Shrager¹, Andrew W. Custer², Katia Kazarinova³, Matthew N. Rasband³, and David Mattson⁴

¹ Department of Neurobiology and Anatomy; ² Neuroscience Graduate Program; ³ Department of Biophysics; and ⁴ Department of Neurology, University of Rochester Medical Center, Rochester, New York 14642

Shrager, Peter, Andrew W. Custer, Katia Kazarinova, Matthew N. Rasband, and David Mattson. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J. Neurophysiol. 79: 529-536, 1998. 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 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 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.

This article has been cited by other articles:

				M. J. Craner, B. C. Hains, A. C. Lo, J. A. Black, and S. G. Waxman Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE Brain, February 1, 2004; 127(2): 294 - 303. [Abstract] [Full Text] [PDF]

				M. Renganathan, T. R. Cummins, W. N. Hormuzdiar, J. A. Black, and S. G. Waxman Nitric Oxide Is an Autocrine Regulator of Na+ Currents in Axotomized C-Type DRG Neurons J Neurophysiol, April 1, 2000; 83(4): 2431 - 2442. [Abstract] [Full Text] [PDF]