The interaction between P2X7Rs and T-type calcium ion channels in penicillin-induced epileptiform activity

Abstract Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels play in the effect of P2X7Rs on penicillin-induced epileptiform activity. In the first set of experiments, P2X7R agonist BzATP (at 25-, 50-, 100- and 200-μg doses), P2X7R antagonist A-438079 (at 5-, 10-, 20- and 40-μg doses) and T-type calcium ion channel antagonist, NNC-550396 were administered for electrophysiological analyses 30 min after penicillin injection (2.5 μl, 500 IU). In the second set of experiments, the effective doses of these substances were used for biochemical analyses. Malondialdehyde (MDA), advanced oxidation protein product (AOPP), glutathione (GSH), glutathione reductase (GR), glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) levels were measured in the cerebrum, cerebellum and brainstem of rats. BzATP (100 μg, icv) increased the mean frequency of epileptiform activity, whereas A-438079 (40 μg, icv) and NNC-550396 (30 μg, ic) reduced it. Both A-438079 and NNC-550396 reversed BzATP's proconvulsant action. BzATP increased lipid peroxidation and protein oxidation; it also altered other antioxidant enzymes measured in this study, which were all then reversed via A-438079 and NNC-550396, at least in the cerebrum. The electrophysiological and biochemical analysis of present study suggest that P2X7Rs and its interaction with T-type calcium ion channels play an important role in the experimental model of epilepsy.