151. The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter.
- Author
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Imaizumi T, Kocsis JD, and Waxman SG
- Subjects
- Animals, Calcium Channel Blockers pharmacology, Calcium Channels drug effects, Cations, Divalent pharmacology, Electric Stimulation, Female, Hypoxia pathology, Membrane Potentials drug effects, Membrane Potentials physiology, Peptides pharmacology, Rats, Rats, Wistar, Sodium-Calcium Exchanger physiology, Sodium-Potassium-Exchanging ATPase metabolism, Spinal Cord drug effects, omega-Conotoxin GVIA, Axons pathology, Calcium Channels physiology, Hypoxia physiopathology, Ion Channel Gating, Spinal Cord pathology, omega-Conotoxins
- 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., (Copyright 1999 Elsevier Science B.V.)
- Published
- 1999
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