title: Modulation of CaM kinase II activity is coincident with induction of status epilepticus in the rat pilocarpine model.
abstract: OBJECTIVE
  This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE).
  
  
  METHODS
  The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity.
  
  
  RESULTS
  After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus.
  
  
  CONCLUSIONS
  The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0599, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Singleton
authors.forename: William H
authors.initials: WH
authors.lastname: Holbert
authors.forename: Anh Tuyet
authors.initials: AT
authors.lastname: Lee
authors.forename: James M
authors.initials: JM
authors.lastname: Bracey
authors.forename: Severn B
authors.initials: SB
authors.lastname: Churn
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013569:Synapses / Q000201:enzymology; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D010455:Peptides; C405629:autocamtide 3; D010862:Pilocarpine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases