Role of L-type calcium channel modulation in nonconvulsive epilepsy in rats.
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.
van Luijtelaar
E L
EL
NICI, Department of Psychology, University of Nijmegen, The Netherlands.
Ates
N
N
Coenen
A M
AM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects*; D004832:Epilepsy, Absence / Q000503:physiopathology*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D015220:Calcium Channels; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester