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

Abstract

Previous studies have shown that (1) removal of extracellular Na+ reduces the anoxia-induced depolarization in neurons and (2) blockade of Na+ channels with TTX attenuates the anoxia-induced depolarization in CA1 neurons in hippocampal slices. The influx of extracellular Na+ during the anoxic depolarization (AD) may link to neuronal injury. To examine the possible role of TTX-sensitive Na+ channels in the Na+ influx into neurons during AD, we measured the effect of tetrodotoxin (TTX) on the extracellular sodium activity ([Na+]e) in hippocampal slices during acute hypoxia with or without glucose-deprivation. We recorded Na+ activity extracellularly from the CA1 region of the stratum pyramidale in hippocampal slices; monitored changes in direct current (DC) potential and extracellular evoked potential with periodic stimulation of Schaffer collateral pathway. We found that TTX (0.1–1 ÌM) delayed the occurrence of AD in which rapid changes in [Na+]e and DC potential were observed. Also, TTX reduced peak changes in both [Na+]e and DC potential during AD induced by oxygen deprivation. The effect of TTX was dose-dependent and was attenuated with the reduction of extracellular glucose during anoxia. We conclude that the homeostasis of [Na+]e of CA1 hippocampal neurons are improved by reducing the activity of TTX-sensitive channels during anoxia and that the mechanistic act of TTX is energy-dependent.