Magnesium removal induces paroxysmal neuronal firing and NMDA receptor-mediated neuronal degeneration in cortical cultures

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Abstract

Removal of extracellular Mg2+ triggered the onset of repetitive excitatory discharges in cultured murine cortical neurons, detected by recording with patch electrodes in the whole cell configuration. The discharges were suppressed by 100 μM d-2-amino-5-phosphonovalerate. Over the next 24–72 h substantial numbers of neurons, but not glia, degenerated, releasing lactate dehydrogenase to the bathing medium. The neuronal death induced by removal of extracellular Mg2+ could be attenuated by either 3 μM tetrodotoxin or 50 μM dextrorphan, and thus likely reflects excessive activation of N-methyl-d-aspartate receptors triggered by excitatory discharges. This Mg2+ removal model may be a useful model in which to study certain aspects of epileptic neocortical injury.

Keywords

Glutamate
Epilepsy
Seizure
Neurotoxicity
Excitatory amino acid
Cortex
Cell culture

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