Related Experiment Video
Updated: Aug 19, 2026

Generation of Local CA1 γ Oscillations by Tetanic Stimulation
Published on: August 14, 2015
Opposite effects of T- and L-type Ca(2+) channels blockers in generalized absence epilepsy
G van Luijtelaar1, D Wiaderna, C Elants
1NICI, Department of Comparative and Physiological Psychology, Psychology Laboratory, Nijmegen University, PO Box 9104, 6500 HE, Nijmegen, Netherlands. luitelaar@nici.kun.nl
Abstract:
The role of the T-type Ca(2+) channel blocker, ethosuximide, the L-type Ca(2+) channel blocker, nimodipine and L-type Ca(2+) channel opener, BAY K8644 (1,4 Dihydro-2, 6-dimethyl-5-nitro-4-[trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester), was investigated on spike-wave discharges in WAG/Rij rats. This strain is considered as a genetic model for generalized absence epilepsy. A dose-dependent decrease in the number of spike-wave discharges was found after i.c.v. ethosuximide, an increase after i.p. nimodipine and 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 conotoxins, MVIIC and GVIA, which block P/Q-type and N-type Ca(2+) channels, respectively. Only after i.c.v. administration of omega-conotoxin GVIA were the number and duration of spike-wave discharges reduced, but animals showed knock-out lying. The latter suggests behavioural or toxic effects and that the decrease in spike-wave activity cannot unequivocally be attributed to blockade of N-type Ca(2+) channels. It can be concluded that T- and L-type Ca(2+) 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 mechanisms.
Insights
Ethosuximide (T-type calcium channel blocker) and BAY K8644 (L-type calcium channel opener) reduced absence epilepsy seizures in rats. Nimodipine (L-type blocker) increased seizures, suggesting complex roles for calcium channels in epilepsy.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Absence epilepsy is a neurological disorder characterized by spike-wave discharges.
- WAG/Rij rats are a genetic model for studying generalized absence epilepsy.
- Calcium channels play a critical role in neuronal excitability and epilepsy.
Purpose of the Study:
- To investigate the effects of T-type and L-type calcium channel modulators on spike-wave discharges in WAG/Rij rats.
- To explore the potential of targeting specific calcium channel subtypes for absence epilepsy treatment.
Main Methods:
- Administration of ethosuximide (T-type blocker), nimodipine (L-type blocker), and BAY K8644 (L-type opener) to WAG/Rij rats.
- Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration routes were used.
- Monitoring and quantification of spike-wave discharges.
- Preliminary investigation with P/Q-type (MVIIC) and N-type (GVIA) conotoxins.
Main Results:
- Ethosuximide and BAY K8644 dose-dependently decreased spike-wave discharges.
- Nimodipine increased spike-wave discharges.
- BAY K8644 antagonized the effects of nimodipine.
- Omega-conotoxin GVIA reduced spike-wave discharges but caused adverse behavioral effects, confounding results.
Conclusions:
- T-type calcium channel blockers and L-type calcium channel openers have opposing effects on absence epilepsy seizures.
- L-type calcium channel blockers appear to exacerbate seizures.
- The role of N-type calcium channels requires further investigation due to confounding factors.
More Related Videos
09:39Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation
Published on: June 7, 2016
07:42Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates
Published on: October 18, 2018
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Antiepileptic Drugs: Sodium Channel Blockers
Sodium channel blockers modulate ion channels, particularly voltage-gated sodium channels. They block only sodium ion movement.
Among the most commonly prescribed antiepileptic drugs are...
Antiepileptic Drugs: Calcium Channel Blockers
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...