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A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus
Author(s) -
Kurz Jonathan E.,
Sheets Dan,
Parsons J. Travis,
Rana Aniruddha,
Delorenzo Robert J.,
Churn Severn B.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00426.x
Subject(s) - calcineurin , okadaic acid , status epilepticus , dephosphorylation , phosphatase , endocrinology , pilocarpine , medicine , chemistry , hippocampus , pharmacology , biology , biochemistry , enzyme , neuroscience , epilepsy , transplantation
This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium‐dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus‐induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p ‐nitrophenol phosphate. A significant status epilepticus‐dependent increase in both basal and Mn 2+ ‐dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 n m okadaic acid, but sensitive to 50 µ m okadaic acid. The increase in basal activity was also resistant to 100 µ m sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found 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 increase in both basal and maximal calcineurin activity.