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

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 mu M) 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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.