The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter.

Abstract

Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.

• Authors: T Imaizumi, J D Kocsis, S G Waxman
• Journal: Brain research (Brain Res) Vol. 817 Issue 1-2 Pg. 84-92 (Jan 30 1999) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9889329 (Publication Type: Journal Article)
• Copyright: Copyright 1999 Elsevier Science B.V.

Chemical References

• Calcium Channel Blockers
• Calcium Channels
• Cations, Divalent
• Peptides
• Sodium-Calcium Exchanger
• omega-Conotoxins
• omega-conotoxin-MVIIC
• omega-Conotoxin GVIA
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Axons (pathology)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (drug effects, physiology)
• Cations, Divalent (pharmacology)
• Electric Stimulation
• Female
• Hypoxia (pathology, physiopathology)
• Ion Channel Gating
• Membrane Potentials (drug effects, physiology)
• Peptides (pharmacology)
• Rats
• Rats, Wistar
• Sodium-Calcium Exchanger (physiology)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Spinal Cord (drug effects, pathology)
• omega-Conotoxin GVIA
• omega-Conotoxins