title: Cellular mechanisms of epilepsy and potential new treatment strategies.
abstract: Over the last 15 years, neurobiologists have begun to unravel the cellular mechanisms that underlie epileptiform activity. Such investigations have two main objectives: (1) to develop new methods for treating, "curing," or preventing epilepsy: and (2) to learn more about the normal functioning of the human brain, at the cellular/molecular and the neurological/psychological levels by analyzing abnormal brain functioning. The electroencephalogram (EEG) spike is a marker for the hyperexcitable cortex and arises in or near an area with a high epileptogenic potential. The depolarizing shift (DS) that underlies the interictal discharge (ID) appears to be generated by a combination of excitatory synaptic currents and intrinsic voltage-dependent membrane currents. The hyperpolarization that follows the DS (post-DS HP) limits ID duration, determines ID frequency, and prevents ID deterioration into seizures. The disappearance of the post-DS HP in some models is related to the onset of seizures and the spread of epileptiform activity. During the transition to seizures, the usually self-limited ID spreads in time and anatomical space. Several processes may intervene in the pathophysiological dysfunction. These include enhancing GABA-mediated inhibition, dampening NMDA-mediated excitability, interfering with specific Ca2+ currents in central neurons, and perhaps stimulating "gating" pathways.
authors: Graduate Hospital, Department of Neurology, Philadelphia, Pennsylvania 19146.
authors: M A
authors: MA
authors: Dichter
mesh_terms: D000200:Action Potentials; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018756:GABA Antagonists; D006801:Humans; D007473:Ion Channels; D011188:Potassium / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium