It is generally considered that epilepsy and seizures are related to alteration in neuronal excitation/ inhibition balance. On the other hand, using an in vi‑ tro isolated guinea pig brain model of focal seizures, it has been shown that seizures start with strong firing of inhibitory interneurons, silence of principal cells, and a massive increase of extracellular potassium concentration. In order to investigate the link between ionic dynamics and experimentally observed seizure pattern, we developed a computational model of hippocampal network embedded in the extracellular space with realistic Na+ , K+ , Cl- , and Ca2+ dynamics, glial cells, and a diffusion mechanism. The model exhibits seizure‑like activity that is qualitatively similar to experimentally observed seizures in the isolated guinea pig brain. We show that, in the model, strong discharge of inhibitory interneurons leads to long lasting accumulation of extracellular potassium, which triggers and sustains abnormal discharges of the neuronal network, including ictal bursting. Using computational modeling, we also suggest novel antiepileptic therapies targeting potassium regulation systems.