A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus

This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineu rin is an important modulator of many neuronal processes, including learnin g and memory, induction of apoptosis, receptor function and neuronal excita bility. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implicat ions; Status epilepticus was induced by pilocarpine injection and allowed t o continue for 60 min. Brain region homogenates were then assayed for calci neurin activity by dephosphorylation of p-nitrophenol phosphate. A signific ant status epilepticus-dependent increase in both basal and Mn2+-dependent calcineurin activity was observed in homogenates isolated from the cortex a nd hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 muM okadaic acid. The increase in basa l activity was also resistant to 100 muM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following sta tus epilepticus. However, the increase in calcineurin activity was not foun d to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant inc rease in both basal and maximal calcineurin activity.