Voltage-gated ion channels (VGICs), extensively distributed in the central nervous system (CNS), are responsible for the generation as well as modulation of neuroexcitability and considered as vital players in the pathogenesis of human epilepsy, with regulating the shape and duration of action potentials (APs). For instance, genetic alterations or abnormal expression of voltage-gated sodium channels (VGSCs), Kv channels, and voltage-gated calcium channels (VGCCs) are proved to be associated with epileptogenesis. This chapter aims to highlight recent discoveries on the mutations in VGIC genes and dysfunction of VGICs in epilepsy, especially focusing on the pathophysiological and pharmacological properties. Understanding the role of epilepsy-associated VGICs might not only contribute to clarify the mechanism of epileptogenesis and genetic modifiers but also provide potential targets for the precise treatment of epilepsy.
Part of the book: Epilepsy
The Hodgkin-Huxley model, at its 66th anniversary, remains a footing stone of neuroscience, which describes how the action potential (AP) is generated. As the core player of AP initiation, voltage-gated sodium channels (VGSCs) are always considered to be required for electrogenesis in excitable cells. Cells which are not traditionally been considered to be excitable, including glial cells, also express VGSCs in physiological as well as pathological conditions. The dysfunction of glial VGSCs is seemingly not related to abnormal excitation of neurons, but of importance in the astrogliosis and M1 polarization of microglia, which could induce refractory neuroinflammatory diseases, such as multiple sclerosis, stroke, epilepsy, and Alzheimer’s and Parkinson’s diseases. Therefore, in this chapter, we aim to describe the physiological and pathological roles of VGSCs contributing to the activity of glial cells and discuss whether VGSC subtypes could be used as a novel drug target, with an eye toward therapeutic implications for neuroinflammatory diseases.
Part of the book: Neuroimaging