title: Effects of polyvalent cations and dihydropyridine calcium channel blockers on recovery of CNS white matter from anoxia.
abstract: The effects of anoxic injury on the functional integrity of mammalian central white matter were studied electrophysiologically using the rat optic nerve model. Previous studies on this model have shown that extracellular Ca2+ is critical to the production of irreversible anoxic injury, and suggest that during anoxia Ca2+ crosses the membrane to enter the intracellular compartment. We attempted to elucidate the mechanism by which this damaging Ca2+ influx occurs. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM) or La3+ (0.1 mM) had no effect on recovery of the area under the compound action potential after a standard 60 min period of anoxia; only Mg2+ (10 mM) significantly improved recovery (54.9 +/- 8.9% vs. 28.7 +/- 10.1%, P less than 0.005). Treatment with organic Ca2+ channel blockers of the dihydropyridine class, nifedipine (1-10 microM) or nimodipine (1-40 microM), also had no effect on recovery from anoxia. We conclude that Ca2+ influx during anoxia does not occur via conventional Ca2+ channels sensitive to polyvalent cations or dihydropyridines.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: P K
authors.initials: PK
authors.lastname: Stys
authors.forename: B R
authors.initials: BR
authors.lastname: Ransom
authors.forename: S G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D009900:Optic Nerve / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D009553:Nimodipine; D009543:Nifedipine; D002118:Calcium