Potassium channels as prominent targets and tools for the treatment of epilepsy

ABSTRACT

Introduction

K⁺ channels are of great interest to epilepsy research as mutations in their genes are found in humans with inherited epilepsy. At the level of cellular physiology, K+ channels control neuronal intrinsic excitability and are the main contributors to membrane repolarization of active neurons. Recently, a genetically modified voltage-dependent K⁺ channel has been patented as a remedy for epileptic seizures.

Areas covered

We review the role of potassium channels in excitability, clinical and experimental evidence for the association of potassium channelopathies with epilepsy, the targeting of K+ channels by drugs, and perspectives of gene therapy in epilepsy with the expression of extra K+ channels in the brain.

Expert Opinion

Control over K+ conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+ channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.

KEYWORDS:

• Epilepsy
• potassium channels
• channelopathies
• gene therapy
• pharmacology

Article highlights

• K+ channels underlie one of the most powerful intrinsic mechanisms of regulation of excitability.

• K+ channel mutations correlate with several types of epilepsy disorders.

• Targeting of K+ channels with drugs or expressing additional K+ channels in the brain is of great potential for the treatment of epilepsy.

• Therapeutic effect of improved potassium conductance is aimed at the reduction of neuronal excitability by activating an outward cationic current.

• Therapeutic interference with such powerful mechanisms of neuronal self-regulation requires being very careful in order not to cause any impairment of normal brain function.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes consultancies, employment, expert testimony, honoraria, speakers bureaus, retainers, stock options or ownership.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by grant RFBR 19-015-00022A and 18-015-00418. The authors research analyzing channel families has been supported by grant RSF 20-15-00408.