Ransom. Axonal L-type Ca 2ϩ channels and anoxic injury in rat CNS white matter. J Neurophysiol 85: 900 -911, 2001. We studied the magnitude and route(s) of Ca 2ϩ flux from extra-to intracellular compartments during anoxia in adult rat optic nerve (RON), a central white matter tract, using Ca 2ϩ -sensitive microelectrodes to monitor extracellular [Ca 2ϩ ] ([Ca 2ϩ ] o ). One hour of anoxia caused a rapid loss of the stimulus-evoked compound action potential (CAP), which partially recovered

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... ng re-oxygenation, indicating that irreversible injury had occurred. After an initial increase caused by extracellular space shrinkage, anoxia produced a sustained decrease of 0.42 mM (29%) in [Ca 2ϩ ] o . We quantified the [Ca 2ϩ ] o decrease as the area below baseline [Ca 2ϩ ] o during anoxia and used this as a qualitative index of suspected Ca 2ϩ influx. The degree of RON injury was predicted by the amount of Ca 2ϩ leaving the extracellular space. Bepridil, 0 Na ϩ artificial cerebrospinal fluid or tetrodotoxin reduced suspected Ca 2ϩ influx during anoxia implicating reversal of the Na ϩ -Ca 2ϩ exchanger as a route of Ca 2ϩ influx. Diltiazem reduced suspected Ca 2ϩ influx during anoxia, suggesting that Ca 2ϩ influx via L-type Ca 2ϩ channels is a route of toxic Ca 2ϩ influx into axons during anoxia. Immunocytochemical staining was used to demonstrate and localize high-threshold Ca 2ϩ channels. Only ␣1 C and ␣1 D subunits were detected, indicating that only L-type Ca 2ϩ channels were present. Double labeling with anti-neurofilament antibodies or anti-glial fibrillary acidic protein antibodies, localized Ltype Ca 2ϩ channels to axons and astrocytes. Address for reprint requests: A. M. Brown,