Opposite effects of T- and L-type Ca2+ channels blockers in generalized absence epilepsy

The role of the T-type Ca2+ channel blocker, ethosuximide, the L-type Ca2channel blocker, nimodipine and L-type Ca2+ channel opener, BAY K8644 (1,4 Dihydro-2,6-dimethyl-5-nitro-4-[trifluoromethyl)-phenyl]-3-pyridine carboxy lic acid methyl ester), was investigated on spike-wave discharges in WAG/Ri j rats. This strain is considered as a genetic model for generalized absenc e epilepsy. A dose-dependent decrease in the number of spike-wave discharge s was found after i.c.v, ethosuximide, an increase after i.p. nimodipine an d a decrease after i.c.v. BAY K8644. BAY K8644 was also able to antagonise the effects of nimodipine. Preliminary data were obtained with two conotoxi ns, MVIIC and GVIA, which block P/Q-type and N-type Ca2+ channels, respecti vely. Only after i.c.v. administration of omega -conotoxin GVIA were the nu mber and duration of spike-wave discharges reduced, bur animals showed knoc k-out lying. The latter suggests behavioural or toxic effects and that the decrease in spike-wave activity cannot unequivocally be attributed to block ade of N-type Ca2+ channels. It can be concluded that T- and L-type Ca2+ channel blockers show opposite effects on spike-wave discharges. Furthermore, these effects are difficult to explain in terms of a model for spindle burst activity in thalamic relay cells proposed by McCormick and Bal [Sleep and arousal: thalamocortical me chanisms. Arm. Rev. Neurosci. 20 (1997) 185]. (C) 2000 Elsevier Science B.V . All rights reserved.