Sodium homeostasis in rat hippocampal slices during oxygen and glucose deprivation: role of voltage-sensitive sodium channels

Abstract

The breakdown in brain ionic homeostasis during energy deprivation (anoxic depolarization [AD]) is intimately linked to neuronal injury. We studied the role of one particular route of Na + influx, voltage-sensitive Na + channels, in the AD induced by O 2 and/or glucose deprivation. We recorded extracellular Na + concentration ([Na +] e) and direct current potential (DCP) in the CA1 stratum pyramidale of hippocampal slices using Na +-selective microelectrodes. Tetrodotoxin (0.1–1 μM) delayed the occurrence of AD and reduced the peak change in both [Na +] e and DCP during AD. However the tetrodotoxin effects were overcome by a concomitant reduction in extracellular glucose during anoxia. We conclude that: (1) the activation of voltage-gated Na + channels is involved in the triggering of AD; (2) there may be a critical level of energy depletion when AD occurs and different mechanisms may underlie AD during hypoxia, compared to O 2 and glucose deprivation.