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; p. 1209
• Main Authors: Parsons, J T, Churn, S B, Kochan, L D, DeLorenzo, R J
• Format: Journal Article
• Language: English
• Published: England 01.09.2000
• Subjects: Animals; Ca(2+) Mg(2+)-ATPase - metabolism; Calcium - metabolism; Cytosol - metabolism; Kinetics; Male; Microsomes - drug effects; Microsomes - metabolism; Pilocarpine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Status Epilepticus - chemically induced; Status Epilepticus - physiopathology; Thapsigargin - pharmacology
• ISSN: 0022-3042
• 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 pilocarpine treated 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.