Potassium Channels in Genetic Epilepsy
Year: 2024
Type: book-chapter
Abstract: The past 70 years have provided a foundation for understanding potassium channel function at the single-channel, cellular, and circuit levels. Basic science of epilepsy has implicated potassium channel dysfunction in the pathogenesis of acquired epilepsy, and, more recently, genetic studies have revealed a large number of variants in potassium channel–encoding genes that cause epilepsy in humans. Identification and functional assessment of these variants have demonstrated they alter protein function, generating several hypotheses for how potassium channel dysfunction leads to the hypersynchronous neural activity characteristic of seizures. However, appreciation of the developmental, cellular, and synaptic complexity of the brain has increased in parallel to our knowledge of potassium channels, complicating the most straightforward idea that potassium channel dysfunction merely leads to depolarization of principal neurons, which causes seizures. The fact that many potassium channel–related epilepsies remain treatment refractory underscores the lack of a mechanistic understanding of this process. This chapter reviews our current understanding of the genetic and functional changes in potassium channels that may lead to epilepsy, within the framework of features of the excitable neuronal membrane known to be controlled by potassium currents. From there, the chapter expands into cell-type-specific roles of potassium channels, their effects on circuit development, and novel molecular interactions, and the evidence that these factors may play a role in epileptogenesis. Finally, the chapter highlights newer experimental approaches that have the potential to clarify the mechanisms through which potassium channel dysfunction leads to epilepsy and pave the way for more effective treatments.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4401032258