Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.
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.
Bracey
James M
JM
Department of Anatomy, Virginia Commonwealth University, Richmond, VA 23298-0599, USA.
Kurz
Jonathan E
JE
Low
Brian
B
Churn
Severn B
SB
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D002908:Chronic Disease; D003292:Convulsants / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003292:Convulsants; D017868:Cyclic AMP-Dependent Protein Kinases; D009479:Neuropeptides; D010862:Pilocarpine; D018091:Receptors, AMPA