TYPES OF ELECTRICAL DISCHARGES IN GENERALIZED SEIZURES AND SITES OF ACTION OF ANTISEIZURE MEDICATIONS
Illustrations of types of electrical discharges in generalized seizures and the sites of action for antiseizure medications that reduce excitability or that enhance inhibition.
A. Paroxysmal depolarization shift (PDS) is a cellular marker of epilepsy and consists of a large depolarization of a group of neurons with action potentials, as indicated by the vertical lines on the large depolarization. The PDS is followed by repolarization. The PDS and repolarization corresponds to a spike and wave on the EEG. A seizure occurs when there is a massive depolarization of cells without intervening periods of repolarization. This would correspond to the tonic phase of the seizure. As inhibition increases during the seizure, there is a cycle of PDS followed by repolarization. This corresponds to the clonic phase of the seizure
B. Examples of molecular targets of antiepileptic drugs that reduce excitability. This may occur through blockage of calcium, sodium, and potassium channels or through reducing ion flow through NMDA and AMPA receptors. Levetiracetam binds to synaptic vesicles, which may lead to reduced neurotrasnmiter release.
C. Examples of molecular targets of antiepileptic drugs that enhance inhibition. Drugs may increase amount of GABA postsynaptically by blocking GABA uptake or increase intracellular GABA by reducing degradation of GABA. Enhancing chloride flow through the GABA receptor is a common mechanism of inhibitory drugs, such as barbiturates and benzodiazepines. Levetiracetam displaces zinc from the GABA receptor, which results in increased chloride currents.