Altered Calcium/Calmodulin Kinase II Activity Changes Calcium Homeostasis That Underlies Epileptiform Activity in Hippocampal Neurons in Culture

Epilepsy is characterized by the occurrence of spontaneous recurrent epileptiform discharges (SREDs) in neurons. A de-crease in calcium/calmodulin-dependent protein kinase II (CaMK-II) activity has been shown to occur with the develop-ment of SREDs in a hippocampal neuronal culture model of acquired epilepsy, and altered calcium (Ca2) homeostasis has been implicated in the development of SREDs. Using antisense oligonucleotides, this study was conducted to determine whether selective suppression of CaMK-II activity, with subse-quent induction of SREDs, was associated with altered Ca2 homeostasis in hippocampal neurons in culture. Antisense knockdown resulted in the development of SREDs and a de-crease in both immunocytochemical staining and enzyme ac-tivity of CaMK-II. Evaluation of [Ca2]i using Fura indicator