title: 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.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06516, USA.
authors.forename: T
authors.initials: T
authors.lastname: Imaizumi
authors.forename: J D
authors.initials: JD
authors.lastname: Kocsis
authors.forename: S G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002413:Cations, Divalent / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D010455:Peptides; D019831:Sodium-Calcium Exchanger; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA; D000254:Sodium-Potassium-Exchanging ATPase