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

This review discusses the current understanding of the molecular mechanisms of pathological hyperexcitation and synchronization of neuronal networks in epileptogenesis, including potassium, GABA, membrane (cellular), and synaptic (network) models. The focus of these models is the disturbance of the balance between excitation and inhibition involving multiple positive and negative feedback loops (PFL/NFL) in neuronal networks. This paper considers current ideas about (1) the robustness of dynamical systems with many NFLs, and (2) degeneracy, i.e., the ability of heterogeneous elements (channels, currents) to replace each other, as the basis for the stable functioning of hyperexcited networks in channelopathies and ion channel hyperexpression. In this work, a potential mechanism of spontaneous seizure onset and potassium accumulation in the intercellular space is proposed; it is based on potassium- and calcium-induced activation of a group of cation channels (HCN, Kir2.x, hERG, Nav1.х, and ВКСа) and ensures the robustness and high sensitivity of epileptiform activity to external and internal factors due to degeneracy and PFLs formation.