NMDA RECEPTOR-DEPENDENT EXCITOTOXICITY - THE ROLE OF INTRACELLULAR CA2(+) RELEASE

Massive activation of glutamate receptors can result in excessive rise s in cytoplasmic Ca2+ that are thought to underlie the fundamental pro cesses ultimately leading to neuronal death. Preventing such cellular Ca2+ rises in the brain may reduce considerably the neuronal damage pr oduced by stroke, head trauma, or epilepsy. Activation of NMDA recepto rs is instrumental in this type of neurotoxicity. Recent findings, dis cussed here by Istvan Mody and John MacDonald, indicate that a large p roportion of the neurotoxic Ca2+ that enters nerve cells following NMD A receptor activation originates from an intracellular Ca2+ pool. The release of Ca2+ from this pool is sensitive to the skeletal muscle rel axant dantrolene, and this may constitute a novel and alternative ther apeutic approach against NMDA receptor-mediated excitotoxicity.