Disparity of cell swelling and rapid neuronal death by excitotoxic insults in rat hippocampal slice cultures.

The rapidly (< 1 h) developing neuronal death induced by a 15-min-exposure to N-methyl-D-aspartate (NMDA) in rat hippocampal slice cultures is associated with cell swelling. We examined whether the swelling directly leads to neuronal death. The rapid neuronal death assayed by propidium iodide was Cl(-)-dependent, as reported for the cell swelling. However, the dose-dependence for NMDA-induced neuronal death differed from that for the cell swelling. Also, cell swelling alone induced by hypotonic insults led to neuronal death only when the cell size increased far more than the extent achieved by NMDA insults. Moreover, contrary to the previous notion, the rapid neuronal death was Ca2+-dependent. Thus, the primary cause of the rapid neuronal death induced by NMDA cannot be attributed to cell swelling.