Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies

• Published in: Pharmacological reviews Vol. 70; no. 1; pp. 142 - 173
• Main Authors: Oyrer, Julia, Maljevic, Snezana, Scheffer, Ingrid E., Berkovic, Samuel F., Petrou, Steven, Reid, Christopher A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Epilepsy - drug therapy; Epilepsy - genetics; Epilepsy - metabolism; Humans; Ion Channels - antagonists & inhibitors; Ion Channels - genetics; Ion Channels - metabolism; Molecular Targeted Therapy; Review; HCN; JME; GGE; CAE; EEG; nAChR; iPSC; NMDA; ADNFLE; GEFS
• ISSN: 0031-6997; 1521-0081; 1521-0081
• DOI: 10.1124/pr.117.014456

Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching—from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies. About 25% of genes identified in epilepsy encode ion channels. Much of our understanding of disease mechanisms comes from work focused on this class of protein. In this study, we review the genetic, molecular, and physiologic evidence supporting the pathogenic role of a number of different voltage- and ligand-activated ion channels in genetic epilepsy. We also review proposed disease mechanisms for each ion channel and highlight targeted therapeutic strategies.