Important role of reverse Na(+)-Ca(2+) exchange in spinal cord white matter injury at physiological temperature.
Spinal cord injury is a devastating condition in which most of the clinical disability results from dysfunction of white matter tracts. Excessive cellular Ca(2+) accumulation is a common phenomenon after anoxia/ischemia or mechanical trauma to white matter, leading to irreversible injury because of overactivation of multiple Ca(2+)-dependent biochemical pathways. In the present study, we examined the role of Na(+)-Ca(2+) exchange, a ubiquitous Ca(2+) transport mechanism, in anoxic and traumatic injury to rat spinal dorsal columns in vitro. Excised tissue was maintained in a recording chamber at 37 degrees C and injured by exposure to an anoxic atmosphere for 60 min or locally compressed with a force of 2 g for 15 s. Mean compound action potential amplitude recovered to approximately 25% of control after anoxia and to approximately 30% after trauma. Inhibitors of Na(+)-Ca(2+) exchange (50 microM bepridil or 10 microM KB-R7943) improved functional recovery to approximately 60% after anoxia and approximately 70% after traumatic compression. These inhibitors also prevented the increase in calpain-mediated spectrin breakdown products induced by anoxia. We conclude that, at physiological temperature, reverse Na(+)-Ca(2+) exchange plays an important role in cellular Ca(2+) overload and irreversible damage after anoxic and traumatic injury to dorsal column white matter tracts.
Loeb Health Research Institute, Ottawa Hospital-Civic Campus, University of Ottawa, Ottawa, Ontario K1Y 4K9, Canada.
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D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D019831:Sodium-Calcium Exchanger / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013696:Temperature; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D019831:Sodium-Calcium Exchanger; D015764:Bepridil; D013890:Thiourea