Prolonged changes in Ca2+/calmodulin-dependent protein kinase II after a brief pentylenetetrazol seizure; potential role in kindling.
This study evaluated the alteration of CaMKII autophosphorylation and distribution in rat brain following a single, brief pentylenetetrazol (PTZ) seizure and during PTZ kindling. Total CaMKII alpha subunit (alpha-CaMKII) and alpha-CaMKII phosphorylated at Thr(286) were detected by immunoblot. A large decrease in CaMKII Thr(286) phosphorylation, as well as CaMKII translocation from particulate to soluble fraction was observed in both cerebral cortex and hippocampus 0.5-4 h after the brief PTZ convulsion. These changes reverted to control values by 12 h. These long-lasting changes in CaMKII autophosphorylation and subcellular distribution after a brief seizure suggested that CaMKII could be involved in carrying forward the signal resulting from brief seizure activity, at least for a few hours, as would be required for kindling to occur. In PTZ kindled rats, convulsions produced changes in CaMKII Thr(286) phosphorylation and distribution in the same direction and of similar magnitude as after the acute convulsion, but lasting for a much longer time. In fact, reduced Thr(286) phosphorylation of alpha-CaMKII was observed up to 48 h, completely bridging the interval between PTZ injections. Similar, but intermediate changes were found in tissue from rats that were only partially kindled. These results implicate CaMKII as a molecular messenger in the acquisition of PTZ kindling.
Dong
Yu
Y
Department of Pharmacology and Therapeutics, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA.
Rosenberg
Howard C
HC
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology*; D013995:Time
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010433:Pentylenetetrazole