Extracellular Potassium Dynamics and Epileptogenesis

Publisher Summary Epilepsy is one of the most common neurological disorders. This chapter describes how recent computational models of cortical circuits with extracellular potassium concentration ([K+]o) dynamics help to overcome the limitations in the understanding of mechanistic understanding of ion concentration dynamics and epileptogenesis, and contribute towards a more refined and experimentally testable theory of [K+]o dynamics and epilepsy. It begins with a discussion of the cortical origin of neocortical paroxysmal oscillations, in vivo and in vitro experiments concerning [K+]o dynamics, and the cortical network model with [K+]o dynamics. Following this, it describes single cell dynamics including detailed bifurcation analysis of a novel bistability with hysteresis between tonic spiking and slow bursting mediated by [K+]o. Furthermore, it extends the model to the network level and describe mechanisms underlying slow state transitions between two distinct oscillatory firing modes (slow bursting and fast run). The transitions between episodes of slow bursting and fast run observed in the model exhibit the same qualitative features as those recorded in vivo during neocortical electrographic seizures in cat and in human patients with the Lennox-Gastaut syndrome. Thereafter, it elucidates the mechanisms of seizure cessation. It concludes by discussing the novel insights derived from computational models and the potential implications for clinical research.