High-Voltage-Activated Calcium Channels in Epilepsy

Abstract Voltage-gated calcium channels support an array of fundamental biological processes in various systems. In the brain, they determine neuronal responses to stimulation, dendritic properties, neuronal firing mode, and synaptic release. They also regulate multiple critical developmental processes, including neuronal proliferation, migration, connectivity, and structural activity-dependent plasticity. For these reasons, mutations in voltage-gated calcium channels result in a variety of neurological disorders displaying epilepsy as a core feature. This chapter summarizes the molecular, cellular, and network mechanisms by which mutations in high-voltage-activated calcium channels result in epilepsy, with a particular focus on CaV1.2 (CACNA1C), CaV1.3 (CACNA1D), CaV2.1 (CACNA1A), and CaV2.3 (CACNA1E)-associated disorders.