Pilocarpine‐Induced Status Epilepticus Causes N ‐Methyl‐D‐Aspartate Receptor‐Dependent Inhibition of Microsomal Mg 2+ /Ca 2+ ATPase‐Mediated Ca 2+ 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: 01.09.2000
• 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 Ca 2+ . To elucidate the mechanisms associated with changes of cytosolic Ca 2+ after status epilepticus, this study was initiated to evaluate the effect of pilocarpine‐induced status epilepticus on Mg 2+ /Ca 2+ ATPase‐mediated Ca 2+ uptake in microsomes isolated from rat cortex, because the Ca 2+ uptake mechanism plays a major role in regulating intracellular Ca 2+ levels. The data demonstrated that the initial rate and overall Ca 2+ 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 Ca 2+ uptake caused by status epilepticus was not an artifact of increased Ca 2+ release from microsomes, selective isolation of damaged microsomes from the homogenate, or decreased Mg 2+ /Ca 2+ ATPase protein in the microsomes. Pretreatment with the NMDA antagonist dizocilpine maleate blocked status epilepticus‐induced inhibition of the initial rate and overall Ca 2+ uptake. The data suggest that inhibition of microsomal Mg 2+ /Ca 2+ ATPase Ca 2+ uptake is involved in NMDA‐dependent deregulation of cytosolic Ca 2+ homeostasis associated with status epilepticus.