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

Abstract

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 Land 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 of 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 Land T-type Ca 2+ 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.

Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy

“…Pharmacological modulation of the spike-wave activity using calcium channel blockers and activators has been shown in animals genetically predisposed to absence seizures. In particular, intraperitoneal and intracerebroventricular microinjections of L-type blockers resulted in an increase in the number and duration of SWDs, but intracortical microinjections suppressed SWDs [ 139 , 140 ].…”

Ethosuximide Affects Paired-Pulse Facilitation in Somatosensory Cortex of WAG\Rij Rats as a Model of Absence Seizure

“…Potassium channels led to the amplification of the hyperpolarization in neurons and activated T-type calcium channels and in fluxed calcium ions into the cell through these channels leading to burst activity of glutamatergic neurons. 11 Sadighi et al (2013) indicated that after PMA injectionan agonist of T-type calcium channels-into the somatosensory cortex, the number and duration of SWDs increased significantly in WAG/Rij rats. 21 In line with our study, an experiment on thalamus using voltage-clamp techniques implied that Ethosuximide reduces low-threshold calcium currents by cutting down the number of LTCC available channels, or creates a change in transduction across LTCC channels.…”

“…11 Sadighi et al (2013) indicated that after PMA injectionan agonist of T-type calcium channels-into the somatosensory cortex, the number and duration of SWDs increased significantly in WAG/Rij rats. 21 In line with our study, an experiment on thalamus using voltage-clamp techniques implied that Ethosuximide reduces low-threshold calcium currents by cutting down the number of LTCC available channels, or creates a change in transduction across LTCC channels. 22,23 Another study showed that microinfusion of 20 nmol of ETX into S1po in freely moving manner GAERS resulted in rapid and almost perfect suppression of SWDs in the whole cortex among both hemispheres compared to systemic administration of the drug.…”

The cardiac effects of carbon nanotubes in rat

“…After these stages, the recorded data from before and after drug injection is analyzed and compared with each other. Since the injection of saline as control group had no significant effect on EEG and ECG recording in pervious papers of our college, 17 - 19 we used our prior data about the effect of saline injection. Therefore, we had no additional group for saline injection as control; the group before injection of CNT was considered as control group.…”