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

Authors


Address correspondence and reprint requests to Dr. S.B. Churn at Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298–0599, U.S.A. E-mail: SCHURN@HSC.VCU.EDU

Abstract

Summary: 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.

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