Chronic inhibition of cortex microsomal Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake in the rat pilocarpine model following epileptogenesis.
In the rat pilocarpine model, 1 h of status epilepticus caused significant inhibition of Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake in cortex endoplasmic reticulum (microsomes) isolated immediately after the status episode. The rat pilocarpine model is also an established model of acquired epilepsy. Several weeks after the initial status epilepticus episode, the rats develop spontaneous recurrent seizures, or epilepsy. To determine whether inhibition of Ca(2+) uptake persists after the establishment of epilepsy, Ca(2+) uptake was studied in cortical microsomes isolated from rats displaying spontaneous recurrent seizures for 1 year. The initial rate and total Ca(2+) uptake in microsomes from epileptic animals remained significantly inhibited 1 year after the expression of epilepsy compared to age-matched controls. The inhibition of Ca(2+) uptake was not due to individual seizures nor an artifact of increased Ca(2+) release from epileptic microsomes. In addition, the decreased Ca(2+) uptake was not due to either selective isolation of damaged epileptic microsomes from the homogenate or decreased Mg(2+)/Ca(2+) ATPase protein in the epileptic microsomes. The data demonstrate that inhibition of microsomal Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake in the pilocarpine model may underlie some of the long-term plasticity changes associated with epileptogenesis.
Parsons
J T
JT
Department of Neurology, Medical College of Virginia Commonwealth University, Richmond, Virginia 23298-0599, USA. jparsons@hsc.vcu.edu
Churn
S B
SB
DeLorenzo
R J
RJ
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007158:Immunologic Techniques; D008861:Microsomes / Q000378:metabolism*; D010862:Pilocarpine; D051381:Rats; D012016:Reference Values; D013997:Time Factors
D002121:Calcium Channel Blockers; D010862:Pilocarpine; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium