Role of Potassium Ion Channels in Epilepsy: Focus on Current Therapeutic Strategies.

Abstract

Epilepsy is one of the prevalent neurological disorders characterized by disrupted synchronization between inhibitory and excitatory neurons. Disturbed membrane potential due to abnormal regulation of neurotransmitters and ion transport across the neural cell membrane significantly contributes to the pathophysiology of epilepsy. Potassium ion channels (KCN) regulate the resting membrane potential and are involved in neuronal excitability. Genetic alterations in the potassium ion channels (KCN) have been reported to result in the enhancement of the release of neurotransmitters, the excitability of neurons, and abnormal rapid firing rate, which lead to epileptic phenotypes, making these ion channels a potential therapeutic target for epilepsy. The aim of this study is to explore the variations reported in different classes of potassium ion channels (KCN) in epilepsy patients, their functional evaluation, and therapeutic strategies to treat epilepsy targeting KCN. A review of all the relevant literature was carried out to compile this article. A large number of variations have been reported in different genes encoding various classes of KCN. These genetic alterations in KCN have been shown to be responsible for disrupted firing properties of neurons. Antiepileptic drugs (AEDs) are the main therapeutic strategy to treat epilepsy. Some patients do not respond favorably to the AEDs treatment, resulting in pharmacoresistant epilepsy. Further to address the challenges faced in treating epilepsy, recent approaches like optogenetics, chemogenetics, and genome editing, such as clustered regularly interspaced short palindromic repeats (CRISPR), are emerging as target-specific therapeutic strategies.