Channeling epilepsy’s hyper-active potential

Epilepsy is a brain disorder defined by a person having two or more unprovoked seizures. Most seizures are caused by hyper excitable neuronal activity and may affect a number of behaviors, including motor, sensory, cognitive or autonomic functions. A broad range of seizure types can occur, and many are linked to mutations in ion channels. This review focuses on four ion channel mutations directly related to major forms of epilepsy. Mutations in the voltage-gated sodium channel cause prolonged sodium influx, which lead to extended depolarization. Voltage-gated potassium channel mutations lead to a slow repolarization during the refractory period, and lead to repeated action potentials. Mutations in the ligand-gated nicotinic acetylcholine receptor cause increased sensitivity to acetylcholine activation and overexcite the thalamo-cortical loop. Mutations in the ionotropic GABAA receptor can accelerate decay of phasic GABA currents and decrease tonic, non-synaptic currents. More recent studies have also looked into the role of glial cells in epilepsy pathology, as they are responsible for the uptake of synaptic glutamate. Activated glia in epileptic loci may also exaggerate neuron excitability through an enhanced rate of glutamate release. While treatment for epilepsy includes medication, vagus nerve stimulation, surgery, and a specialized ketogenic diet, innovative new treatments are currently being developed, such as photoregulation of GABAA receptors.