Old male Wistar rats spontaneously showing hundreds of spike-wave discharges daily were used to investigate the role of
calcium ions in nonconvulsive
epilepsy. The effects of the
L-type calcium channel blocker
nimodipine and the L-type channel opener
BAY K 8644 on number and duration of these spike-wave discharges were investigated. In rats aged 84-94 weeks standard EEG
electrodes were chronically implanted; animals were allowed to recover for 10 days. After a baseline registration,
nimodipine 2.2, 8.8, and 35.2 mg/kg or
BAY K 8644 in dosages of 0.12, 0.47, and 1.88 mg/kg was administered. A control group received the
solvent. EEG recordings were made to evaluate
drug effects. The highest dose of
nimodipine increased the number of spike-wave discharges, whereas
BAY K 8644 reduced the number of spike-wave discharges dose dependently. The highest dose of
BAY K 8644 also induced fatal convulsions in 3 animals. Our results demonstrate that the L-type
calcium antagonist
nimodipine facilitates spike-wave discharges and that the L-type
calcium agonist
BAY K 8644 protects against these discharges, in contrast to previous results suggesting that
calcium channel blockers act as
antiepileptic drugs (AEDs) and that
calcium channel openers act as
convulsants. Our results are a further example of the different pharmacologic profile of convulsive and nonconvulsive
epilepsy and are also in contrast to what has been described for
T-type calcium channel modulation. We therefore propose that modulation of L-type and
T-type calcium channels have opposite effects in nonconvulsive
epilepsy.