Epilepsy research at the University of Washington has a long history. The studies have had a strong clinical, as well as basic science orientation. This Program Project application represents the continuing efforts of a large group of investigators to study basic mechanisms underlying epileptiform phenomena. A pervading theme of the Project is the examination of if, and how the mechanisms of epileptiform activity studied in animal models elucidate underlying processes in the human epileptic focus. Many of the Program Project investigators will use in vitro techniques to examine properties of chronic epileptic foci in two animal models - the kainate-treated rat and the alumina gel-treated monkey - in order to compare properties of those tissues to the properties of tissue removed from human epileptic brain during surgical resections for intractable seizure. Among this group are the studies on, 1) structure and function of Na,K- ATPase, 2) receptor binding studies of excitatory and inhibitory amino acid neurotransmitters, 3) electrophysiological properties and morphological correlates of epileptic neurons, and 4) dihydropyridine-binding calcium channels. Supplementing these experiments are the studies on the human epileptic brain itself (single unit activity in the epileptic focus, and electrophysiological correlates of attention in patients with epilepsy). Another major theme of the Program Project is the involvement of calcium and calcium-related processes in generation of epileptiform activity. We will use electrophysiological analyses to seek functional correlates of the calcium channel studies will carry out electromicroscopic examination of intracellular calcium distribution; and will examine the effects of organic calcium channel blockers as anticonvulsant agents.
