Role of L- and T-Type Calcium Channels in Regulation of Absence Seizures in Wag/Rij Rats

In chronic experiments on five groups of WAG/Rij rats (a genetic model of absence epilepsy; six animals in each group), we recorded EEG activity from the S1po cortical area through implanted electrodes and subjected the cortex to the action of four agents affecting L- and T-type calcium channels (injections through an implanted cannula). A blocker of L-type channels, verapamil hydrochloride, an agonist of these channels, Bay K8644, an antagonist of T-type calcium channels, L-ascorbate, and an agonist of the latter channels, PMA, were used. The parameters of 7- to 10-Hz spike-wave discharges, SWDs, spontaneously generated in the cortex of this rat strain (frequency within SWDs, mean duration of the latter, and their number) were measured within the baseline interval (before injections) and within three subsequent 20-min-long post-injection intervals. Normal saline was injected in the control group. There were no significant differences in the mean peak frequency in SWDs between all examined groups (P > 0.05 in all cases). Verapamil significantly (by more than 40%; P < 0.05) decreased the mean SWD duration throughout the entire period of post-injection observation. The dynamics of the Bay K8644 effects were rather similar, but the intensity of SWD duration changes was somewhat smaller. Both the above agents in the doses used dramatically decreased the number (frequency of appearance) of SWDs within the observation period. L-ascorbate also suppressed SWD generation. The duration of these phenomena decreased mildly, while their number dropped dramatically. In the PMA group, the number of SWDs increased significantly (by 50%, P < 0.05) within the first 20-min-long interval, but this was not observed within subsequent intervals. These findings confirm that blocking or activating of L- and T-type Ca2+ channels in the S1po area (cortical focus area) can significantly control generation of SWDs during absence seizures. Possible mechanisms underlying actions of the tested agents are discussed.