Seizure-Induced AMPA Receptor Phosphorylation, Journal Of Neuroscience

Main Category: Pediatrics / Children's Health
Also Included In: Epilepsy;  Psychology / Psychiatry;  Neurology / Neuroscience
Article Date: 06 Aug 2008 - 4:00 PST

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Seizures in neonates are usually caused by hypoxia and can increase risk of later epilepsy and cognitive impairment. Rakhade et al. induced hypoxic seizures in early postnatal rats to identify molecular changes that increase seizure susceptibility.

Seizures increased the amplitude and frequency of miniature and spontaneous EPSCs mediated by AMPA receptors (AMPARs) within 1 h. This increase likely resulted from increased phosphorylation of AMPAR subunits by PKA, PKC, and calcium/calmodulin-dependent kinase II, because the activity of these kinases was elevated. Phosphorylation of GluR1 was increased at sites that increase channel conductance and synaptic insertion, whereas GluR2 was phosphorylated at a site that leads to its internalization.

GluR1 internalization can increase the number of calcium-permeant AMPA receptors, which could further increase excitability. In vivo treatment with AMPAR antagonists blocked increases in both phosphorylation and EPSC amplitude and frequency, and also attenuated susceptibility to later seizures.

Journal of Neuroscience

The Journal of Neuroscience is the official journal of the Society for Neuroscience. The Journal publishes papers on a broad range of topics of general interest to those working on the nervous system.

Journal of Neuroscience