A balance between excitation and inhibition is necessary to maintain stable brain network dynamics. Traditionally, seizure activity is believed to arise from the breakdown of this delicate balance in favor of excitation with loss of inhibition. Surprisingly, recent experimental evidence suggests that this conventional view may be limited, and that inhibition may play a prominent role in the development of epileptiform synchronization. Our studies, combining biophysical network models and electrophysiology, revealed that the coupled dynamics of sodium and potassium ions play critical role in the development and termination of seizures. We proposed and tested a hypothesis that increase of interneuron firing may trigger biophysical mechanisms promoting accumulation of the extracellular potassium and leading to epileptiform ictal activity. These findings predict a new avenue for pharmacological interventions in patients suffering from intractable epilepsy due to K+ channelopathies.