Important role of reverse Na(+)-Ca(2+) exchange in spinal cord white matter injury at physiological temperature.

Abstract

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.

• Authors: S Li, Q Jiang, P K Stys
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 84 Issue 2 Pg. 1116-9 (Aug 2000) ISSN: 0022-3077 [Print] United States
• PMID: 10938336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
• Calcium Channel Blockers
• Sodium-Calcium Exchanger
• Bepridil
• Thiourea

Topics

• Animals
• Bepridil (pharmacology)
• Blotting, Western
• Calcium Channel Blockers (pharmacology)
• Hypoxia (metabolism)
• In Vitro Techniques
• Male
• Nerve Fibers (chemistry, metabolism)
• Rats
• Rats, Long-Evans
• Sodium-Calcium Exchanger (analysis, antagonists & inhibitors, metabolism)
• Spinal Cord (chemistry, cytology, metabolism)
• Spinal Cord Injuries (metabolism)
• Temperature
• Thiourea (analogs & derivatives, pharmacology)