How does too much glutamate kill a neuron? · Grey Matter

When glutamate stays high, its receptors stay open: sodium, chloride and water rush in and neurons swell within minutes, and calcium floods in through NMDA receptors and voltage-gated calcium channels.

How does too much glutamate kill a neuron?

When glutamate stays high, its receptors stay open: sodium, chloride and water rush in and neurons swell within minutes, and calcium floods in through NMDA receptors and voltage-gated calcium channels. Experiments in cultured neurons showed that removing sodium prevents the swelling but the cells still die later unless calcium is removed too, so calcium is the lethal part. The excess calcium activates proteases and lipases, drives nitric oxide synthase, and overloads the mitochondria until they fail and release signals for cell death, producing reactive oxygen species on the way. Olney named the process excitotoxicity in 1969, and it is the shared final step of damage in stroke, trauma and prolonged seizures.