Effects of polyvalent cations and dihydropyridine calcium channel blockers on recovery of CNS white matter from anoxia

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 < 0.005). Treatment with organic Ca²⁺ channel blockers of the dihydropyridine class, nifedipine (1-10 μM) or nimodipine (1-40 μM), 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. © 1990.