Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus

James M. Bracey, Jonathan E. Kurz, Brian Low, Severn B. Churn*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalBrain research
Volume1283
DOIs
StatePublished - Aug 4 2009

Keywords

  • EEG
  • Glutamate receptor
  • Late long-term potentiation
  • Phosphorylation
  • Time-course

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus'. Together they form a unique fingerprint.

  • Cite this