Status epilepticus results in an N-methyl-D-aspartate receptor-dependent inhibition of Ca2+/calmodulin-dependent kinase II activity in the rat

Status epilepticus is a major medical emergency that results in significant alteration of neuronal function. Status epilepticus involves seizure activ ity recurring frequently enough to induce a sustained alteration in brain f unction. This study was initiated to investigate how status epilepticus aff ects the activity of calcium and calmodulin-dependent kinase II in the brai n. Calcium and calmodulin-dependent kinase II is a neuronally enriched sign al transducing system involved in the regulation of neurotransmitter synthe sis and release, cytoskeletal function, gene transcription, neurotransmitte r receptor function and neuronal excitability. Therefore, alteration of thi s signal transduction system would have significant physiological effects. Status epilepticus was induced in rats by pilocarpine injection, allowed to progress for 60 min and terminated by repeated diazepam injections. Animal s were killed at specific time-points and examined for calcium and calmodul in-dependent kinase LI activity. Calcium and calmodulin-dependent kinase II activity was significantly reduced in cerebral cortex and hippocampal homo genates obtained from status epilepticus rats when compared with control an imals. Once established, the status epilepticus-induced inhibition of calci um and calmodulin-dependent kinase II activity was observed at all time-poi nts tested following the termination of seizure activity. However, calcium and calmodulin-dependent kinase II activity was not significantly decreased in thalamus and cerebellar homogenates. In addition, status epilepticus-in duced inhibition of calcium and calmodulin-dependent kinase II activity was dependent upon activation of N-methyl-D-aspartate subtype of glutamatergic receptors. Thus, status epilepticus induced a significant inhibition of ca lcium and calmodulin-dependent kinase II activity that involves N-methyl-D- aspartate receptor activation. The data support the hypothesis that inhibition of calcium and calmodulin-d ependent kinase II activity may be involved in the alteration of neuronal f unction following status epilepticus. (C) 1999 IBRO. Published by Elsevier Science Ltd.