Premium
Increased CaM kinase II‐mediated phosphorylation of ampa receptors precedes status epilpeticus
Author(s) -
Schafer Johanna Marlies,
Churn Severn,
Kurz Johnathon,
Low Brian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.790.6
Subject(s) - ampa receptor , phosphorylation , excitatory postsynaptic potential , status epilepticus , neurotransmission , long term potentiation , hippocampal formation , chemistry , neuroscience , receptor , endocrinology , medicine , biology , glutamate receptor , epilepsy , biochemistry
This study was conducted to analyze the change in calcium/calmodulin‐dependent kinase II (CaMK II)‐mediated phosphorylation of AMPA receptors at times points throughout the duration of stats epileptics (SE). The GluR1 subunit of the AMPA receptor is phosphorylated at ser831 by CaMK II; the progression of seizure activity into the continuous seizures of status epilepticus may be due to potentiation of excitatory postsynaptic neurotransmission by AMPA‐receptor‐mediated currents. Methods SE was induced by a pilocarpine injection. At three time‐points of discrete seizures preceding SE, 20 and 40 minutes after the onset of SE, and 24 hours post‐SE, cortical and hippocampal brain regions were isolated into homogenization buffer and used for biochemical studies. Proteins were resolved by SDS‐PAGE and subjected to western blot analysis. GluR1 phosphorylation was assessed using phosphoGluR1‐specific antibodies and computer‐assisted densitometry. Results All time point proceeding and during SE had over a 150% increase in phosphorylation at ser831compared to the controls. The increase in pGluR1 was observed well into overt SE. Although, the last time point, 24 hours post‐SE, did not demonstrate a statistically significant change in phosphorylation levels. Conclusions This data suggests that elevated AMPA‐directed CaMK II activity may increase the functionality of excitatory AMPA receptors prior to and during status epilepticus. At the 24 hour time‐point, GluR1 phosphorylation appeared to return to control levels, suggesting a return of CaMK II activity to normal levels.