Pilocarpine‐Induced Status Epilepticus Causes N‐Methyl‐D‐Aspartate Receptor‐Dependent Inhibition of Microsomal Mg2+/Ca2+ ATPase‐Mediated Ca2+ Uptake

• Published in: Journal of neurochemistry Vol. 75; no. 3; pp. 1209 - 1218
• Main Authors: Parsons, J. Travis, Churn, Severn B., Kochan, Lisa D., DeLorenzo, Robert J.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.09.2000; Blackwell
• Subjects: Biological and medical sciences; Calcium homeostasis; Cortex; Endoplasmic reticulum; Epilepsy; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Medical sciences; MK‐801; Nervous system (semeiology, syndromes); Neurology; Sarco(endo)plasmic reticulum Ca2+‐ATPase; Animal model; Nervous system diseases; Calcium; Pathophysiology; Rat; Enzyme; Epilepsy; Rodentia; Glutamate receptor; Pilocarpine; Cerebral disorder; transporting ATPase; Vertebrata; Mammalia; Animal; Central nervous system disease; Hydrolases; NMDA receptor; Endoplasmic reticulum; Ca
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0751209.x

: Status epilepticus is associated with sustained and elevated levels of cytosolic Ca2+. To elucidate the mechanisms associated with changes of cytosolic Ca2+ after status epilepticus, this study was initiated to evaluate the effect of pilocarpine‐induced status epilepticus on Mg2+/Ca2+ ATPase‐mediated Ca2+ uptake in microsomes isolated from rat cortex, because the Ca2+ uptake mechanism plays a major role in regulating intracellular Ca2+ levels. The data demonstrated that the initial rate and overall Ca2+ uptake in microsomes from pilocarpinetreated animals were significantly inhibited compared with those in microsomes from saline‐treated control animals. It was also shown that the inhibition of Ca2+ uptake caused by status epilepticus was not an artifact of increased Ca2+ release from microsomes, selective isolation of damaged microsomes from the homogenate, or decreased Mg2+/Ca2+ ATPase protein in the microsomes. Pretreatment with the NMDA antagonist dizocilpine maleate blocked status epilepticus‐induced inhibition of the initial rate and overall Ca2+ uptake. The data suggest that inhibition of microsomal Mg2+/Ca2+ ATPase Ca2+ uptake is involved in NMDA‐dependent deregulation of cytosolic Ca2+ homeostasis associated with status epilepticus.