Changes in [Ca²⁺]_o during anoxia in CNS white matter

IRREVERSIBLE anoxic injury of axons in the rat optic nerve requires the presence of extracellular Ca²⁺. To test the hypothesis that Ca²⁺ enters an intracellular compartment during anoxia we monitored [Ca²⁺]₀ in this CNS white matter tract using ion-sensitive microelectrodes. Periods of anoxia lasting 15 min resulted in a rapid, reversible increase in [Ca²⁺]₀ accompanied by transient loss of nerve conduction. This increase in [Ca²⁺]₀ was apparently the result of extracellular space shrinkage. Anoxic periods lasting 60 min resulted in an initial rise followed by a sustained fall in [Ca²⁺]₀, indicative of net influx of Ca²⁺ into an intracellular compartment. Following reoxygenation after 60 min of anoxia, [Ca²⁺]₀ slowly returned toward control levels but nerve conduction recovered incompletely, indicating irreversible loss of function. Removal of bath Ca²⁺ lowered [Ca²⁺]₀ to about 100 μM, prevented the anoxia-induced fall in [Ca²⁺]₀, and protected against irreversible loss of the compound action potential.