Involvement of cAMP- and Ca(2+)/calmodulin-dependent neuronal protein phosphorylation in mechanisms underlying genetic predisposition to audiogenic seizures in rats.
It was shown that increased excitability in neurons underlying epilepsies would be maintained by abnormalities in protein phosphorylation systems. This study was initiated to compare the functioning of Ca(2+)/calmodulin- and cAMP-dependent systems of protein phosphorylation in homogenates of neocortex and hippocampus in three animal groups: genetically prone to audiogenic seizures (GPAS) rats, GPAS rats exposed to daily repeated audiogenic seizures (AGPAS rats) and nonepileptic Wistar ones. We found significant differences in phosphorylation of 270, 58, 54 and 42 kDa proteins in neocortex and hippocampus of GPAS rats in comparison with Wistar ones. Daily repeated seizures induced further modifications of phosphorylation of these proteins in only hippocampus of AGPAS rats as compared with GPAS ones. Ca(2+)-independent, functional CAMKII activity was considerably increased in hippocampus but decreased in neocortex of GPAS rats in comparison with Wistar ones. The activity of PKA was increased both in neocortex and hippocampus of GPAS rats. Daily repeated audiogenic seizures induced the decrease of Ca(2+)-independent CAMKII activity in hippocampus and the increase of PKA activity in neocortex of AGPAS rats in comparison with GPAS ones. The present results indicate that modification of 270, 58, 54, and 42 kDa proteins phosphorylation as well as altered CAMKII and PKA activities might be involved in mechanisms of genetic predisposition to audiogenic seizures.
Yechikhov
S
S
Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Pushchino, Moscow, Moscow Region, 142292, Russia. wistar@mail.ru
Morenkov
E
E
Chulanova
T
T
Godukhin
O
O
Shchipakina
T
T
D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020195:Epilepsy, Reflex / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000378:metabolism; D007696:Kindling, Neurologic; D008297:Male; D019579:Neocortex / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012016:Reference Values; D012640:Seizures / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
D002147:Calmodulin; D009419:Nerve Tissue Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium