Modulation of CaM Kinase II Activity Is Coincident with Induction of Status Epilepticus in the Rat Pilocarpine Model

• Published in: Epilepsia (Copenhagen) Vol. 46; no. 9; pp. 1389 - 1400
• Main Authors: Singleton, Michael W., Holbert, William H., Lee, Anh Tuyet, Bracey, James M., Churn, Severn B.
• Format: Journal Article
• Language: English
• Published: 350 Main Street , Malden , MA 02148 , USA and 9600 Garsington Road , Oxford , OX4 2XG , England Blackwell Science Inc 01.09.2005; Blackwell
• Subjects: Animal poisons toxicology. Antivenoms; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Brain Mapping; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; CaM kinase II; Cerebral Cortex - enzymology; Cerebral Cortex - metabolism; Disease Models, Animal; Electroencephalography; Enzyme Inhibitors - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - enzymology; Hippocampus - metabolism; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Muscarinic Agonists - pharmacology; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Neuroprotective agent; Peptides - metabolism; Pharmacology. Drug treatments; Pilocarpine; Pilocarpine - pharmacology; Rats; Rats, Wistar; Status epilepticus; Status Epilepticus - chemically induced; Status Epilepticus - enzymology; Status Epilepticus - metabolism; Subcellular Fractions - drug effects; Subcellular Fractions - enzymology; Synapses - enzymology; Time Factors; Tissue Distribution; Toxicology; Antiglaucomatous agent; Animal model; Agonist; Nervous system diseases; Epilepsy; Furan derivatives; Pilocarpine; CaM kinase II- Status epilepticus- Pilocarpine; Cerebral disorder; Parasympathomimetic; Cholinergic receptor; Subintrant crisis; Modulation; Central nervous system disease; Muscarinic receptor; Status epilepticus
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2005.19205.x

Purpose: 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.