Nitric oxide reversibly impairs axonal conduction in Guinea pig spinal cord.
Increased expression of the inducible and neuronal isoforms of nitric oxide synthase (NOS), and elevated concentrations of nitric oxide (NO) metabolites, are present within the central nervous system (CNS) following neurotrauma and are implicated in the pathogenesis of the accompanying neurologic deficits. We tested the hypothesis that elevated extracellular concentrations of NO introduced by the donor Spermine NONOate, induce reversible axonal conduction deficits in neurons of the guinea pig spinal cord. The compound action potential (CAP) and compound membrane potential (CMP) of excised ventral cord white matter were recorded before, during, and after bathing the tissue (30 min) in varying concentrations (0.25-3.0 mM) of Spermine NONOate. The principal results were a rapid onset, dose-dependent, reduction in amplitude of the CAP (p < 0.05) accompanied by depolarization of the CMP during NO exposure. These effects were largely reversible on washout, at low concentration of the donor (0.5 mM), but were only partially reversed at higher concentrations. Changes in the electrophysiological properties were not evident when the donor had been a priori depleted of NO. The results extend previous reports that NO induces reversible axonal conduction deficits. They provide new evidence of dissociation of the effects of NO on CAP and CMP during washout, and after prolonged exposure to the donor. They add support to the emerging concept that immune-mediated axonal conduction failure contributes to reversible neurologic deficits following neurotrauma and aid in understanding clinical phenomena such as spinal shock and neurologic recovery.
Ashki
Negin
N
Neuroscience Program, University of Western Ontario, London, Ontario, Canada.
Hayes
Keith C
KC
Shi
Riyi
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D046509:Tissue Culture Techniques
D020030:Nitric Oxide Donors; C091861:spermine nitric oxide complex; D013096:Spermine