Evolution of Ideas about the Mechanisms of Neuronal Network Hyperactivation and Burst Firing in Epilepsy. Contribution of Potassium-Induced Activation of Potassium-Conducting Channels to Network Hyperactivation

Abstract

The existing concepts of the molecular mechanisms of pathological hyperexcitability and synchronization of neural networks in epileptogenesis, including potassium, GABA, membrane (cellular) and synaptic (network) models, are discussed. The focus of such models is the imbalance between excitation and inhibition involving numerous positive and negative feedback loops in neural networks. The paper considers modern concepts of (1) the reliability of dynamic systems with a large number of negative feedback loops and (2) the degeneracy, that is, the ability of heterogeneous elements (channels and currents) to replace each other, as the basis for the stable functioning of hyperexcitable networks in channelopathy and hyperexpression of various channels. The paper suggests a possible mechanism for the spontaneous occurrence of convulsive activity and accumulation of potassium in the intercellular space, based on the activation of a group of cationic channels (HCN, K_ir2.x , hERG, Na_v1.х, and BK_Ca), which provides reliability and high sensitivity of epileptiform activity to external and internal factors due to degeneracy and formation of a group of connections of positive feedback loops.