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

• Published in: Journal of neurochemistry Vol. 78; no. 2; pp. 304 - 315
• Main Authors: Kurz, Jonathan E., Sheets, Dan, Parsons, J. Travis, Rana, Aniruddha, Delorenzo, Robert J., Churn, Severn B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2001; Blackwell
• Subjects: Animals; Biological and medical sciences; Brain - enzymology; Calcineurin - metabolism; calcium; calmodulin; Cerebral Cortex - enzymology; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - enzymology; Kinetics; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Nitrophenols - metabolism; NMDA; Organ Specificity; Organophosphorus Compounds - metabolism; phosphatase; Pilocarpine; post‐translational modification; Protein Tyrosine Phosphatases - metabolism; Rats; Rats, Sprague-Dawley; seizure; Seizures - chemically induced; Seizures - physiopathology; Status Epilepticus - chemically induced; Status Epilepticus - enzymology; Status Epilepticus - physiopathology; Substrate Specificity; Nervous system diseases; Calcium; Rat; Enzyme; Phosphoprotein phosphatase; Epilepsy; Rodentia; Furan derivatives; Phosphoric monoester hydrolases; Esterases; Pilocarpine; Cerebral disorder; Vertebrata; Mammalia; Enzymatic activity; Convulsion; Animal; Central nervous system disease; Hydrolases; Calmodulin
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00426.x

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 Mn2+‐dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nm okadaic acid, but sensitive to 50 µm okadaic acid. The increase in basal activity was also resistant to 100 µm 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.