Electrophysiological studies have recently emphasized abnormal synaptic function as an important factor in the generation of seizure discharges. To further delineate these abnormalities, synaptic terminals (synaptosomes) were isolated from brains of animals with seizures. After repeated electroconvulsions (a model used to study the effects of seizures), the level of potassium decreased while that of sodium increased within synaptic terminals because of an enhanced downhill movement of cations. In epileptogenic foci of freezing lesions (a model used to study epileptogenesis), K influx mediated by the Na-K pump was markedly impaired with synaptic terminals. Both pathologic processes in membrane function were corrected by diphenylhydantoin through its stimulation of the Na-K pump. In epileptogenic foci, diphenylhydantoin may also have a direct action on the synapse membrane, apart from its effects on the Na-K pump.
Escueta AV, Appel SH. Brain Synapses: An in Vitro Model for the Study of Seizures. Arch Intern Med. 1972;129(2):333–344. doi:10.1001/archinte.1972.00320020177015
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