Depolarization Block of Neurons During Maintenance of Electrographic Seizures

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Abstract
Epileptic seizures are associated with neuronal hyperactivity. Here, however, we investigated whether continuous neuronal firing is necessary to maintain electrographic seizures. We studied a class of “low-Ca2+” ictal epileptiform bursts, induced in rat hippocampal slices, that are characterized by prolonged (2–15 s) interruptions in population spike generation. We found that, during these interruptions, neuronal firing was suppressed rather than desynchronized. Intracellular current injection, application of extracellular uniform electric fields, and antidromic stimulation showed that the source of action potential disruption was depolarization block. The duration of the extracellular potassium transients associated with each ictal burst was not affected by disruptions in neuronal firing. Application of phenytoin or veratridine indicated a critical role for the persistent sodium current in maintaining depolarization block. Our results show that continuous neuronal firing is not necessary for the maintenance of experimental electrographic seizures.