Role of Ion Concentration Dynamics in Epileptic Seizures

Abstract The regulation of transmembrane ion flux is crucial for maintaining physiological neuronal activity and preventing the occurrence of epileptic seizures. The net effect (e.g., depolarization or hyperpolarization) of the transmembrane ion flux is determined by the relative ion concentration gradients established across the cellular membrane. Because of the tight regulation of neuronal excitability and dynamics by changes in the ion concentrations, the brain has evolved multiple mechanisms to precisely regulate and maintain these concentration gradients. It has been demonstrated that the breakdown in the maintenance of ion gradients may lead to development of seizure discharges and may underly various forms of pathological neuronal activity. It is now well established that during a seizure discharge, the extracellular potassium concentration substantially increases, while the concentrations of extracellular sodium and calcium decrease. More recently, experimental recordings and computational models have demonstrated preictal increases in the intracellular chloride concentration in pyramidal neurons. This chapter discusses the effects of the ion concentration dynamics on seizure initiation, progression, and termination with the goal of providing novel insights into the underlying biophysical mechanisms of epileptic seizures.