Moreover, cGKII regulated epileptic seizures by phosphorylating GluA1 at Ser845 to modulate the expression and function of GluA1 in the postsynaptic membrane.
Our findings indicate that an abnormality in GluA1 palmitoylation can lead to hyperexcitability in the cerebrum, which negatively affects the maintenance of network stability, resulting in epileptic seizures.<b>SIGNIFICANCE STATEMENT</b> AMPARs predominantly mediate excitatory synaptic transmission.
Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.
We showed previously that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) and Serine 845 (S845) sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced posttranslational modifications may represent a novel therapeutic target.
Single-cell RT-PCR found preferential expression of the subunits GluR1 and GluR2 in human astrocytes, and the expression patterns were similar in patients with AHS and lesion-associated epilepsy.