Potassium Channels in Epilepsy

Abstract

This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dynamic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With ∼80 potassium channel types, of which ∼10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models.

Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy

“…Finally, there is also a clear age effect on the form of the epilepsy, which could also interplay. Potassium channel defects are frequently associated with epilepsy [13], and two SCA19 patients from the original Dutch family had myoclonus [3]. The benign epilepsy phenotypes and EEG of the two French families are similar to those previously reported in one patient with a de novo KCND3 mutation who had generalized epilepsy with paroxysmal rhythmic theta waves in frontal and parietal regions [14].…”

Encephalopathies with KCNC1 variants: genotype‐phenotype‐functional correlations

“…Voltage‐gated potassium channels are important in setting membrane resting potential, regulating firing patterns and modifying action potential duration and neurotransmitter release . Mutations in genes encoding voltage‐gated potassium channels have been implicated in several conditions including spinocerebellar ataxia, paroxysmal movement disorders, and various epilepsies …”

Multi-modal characterization and simulation of human epileptic circuitry

“…Yet, gain-of-function of BK exhibited in our patient cohort as well as described in patients of genetic epilepsies has been difficult to explain mechanistically (29)(30)(31). Here, we offer a mechanistic framework relating gain-of-function in BK channels of human granule cells, key regulators of hippocampal excitability (20), with increased network excitability.…”