Chronic inhibition of cortex microsomal Mg2+/Ca2+ ATPase-mediated Ca2+ uptake in the rat pilocarpine model following epileptogenesis

In the rat pilocarpine model, 1 h of status epilepticus caused significant inhibition of Mg2+/Ca2+ ATPase-mediated Ca2+ uptake in cortex endoplasmic r eticulum (microsomes) isolated immediately after the status episode. The ra t pilocarpine model is also an established model of acquired epilepsy. Seve ral weeks after the initial status epilepticus episode, the rats develop sp ontaneous recurrent seizures, or epilepsy. To determine whether inhibition of Ca2+ uptake persists after the establishment of epilepsy, Ca2+ uptake wa s studied in cortical microsomes isolated from rats displaying spontaneous recurrent seizures for 1 year. The initial rate and total Ca2+ uptake in mi crosomes from epileptic animals remained significantly inhibited 1 year aft er the expression of epilepsy compared to age-matched controls. The inhibit ion of Ca2+ uptake was not due to individual seizures nor an artifact of in creased Ca2+ release from epileptic microsomes. In addition, the decreased Ca2+ uptake was not due to either selective isolation of damaged epileptic microsomes from the homogenate or decreased Mg2+/Ca2+ ATPase protein in the epileptic microsomes. The data demonstrate that inhibition of microsomal M g2+/Ca2+ ATPase-mediated W uptake in the pilocarpine model may underlie som e of the long-term plasticity changes associated with epileptogenesis.