August 19, 2022

Study into Potassium Channels Reveals Novel Mechanism Behind Epilepsy, Drug Modulation

Article published by McKelvey School of Engineering

Epilepsy is a neurological disorder that arises from abnormal electrical activity in the brain leading to seizures. These seizure events can have a variety of causes, including genetic variants in a family of proteins that regulate potassium ions in the brain. Researchers at Washington University in St. Louis have led an international team to take a close look at the mechanisms behind the function and dysfunction of these proteins, as well as their interactions with an antiepileptic drug, to develop a potential new strategy to treat epilepsy.

Jianmin Cui, professor of biomedical engineering in the McKelvey School of Engineering, and Nien-Du Yang, a doctoral student in biomedical engineering who conducts research in Cui’s lab, teamed up with Harley Kurata, associate professor of pharmacology at the University of Alberta, and investigated the working mechanism of two potassium ion channels, KCNQ2 and KCNQ3. Their findings uncover a conserved mechanism for KCNQ channel activation that is a target of both epilepsy-linked mutations and a small molecule compound.

The KCNQ potassium channel family has multiple functions, from regulating heartbeat (by KCNQ1) to controlling excitability of neurons (by KCNQ2-5). These channels are voltage-activated so that they sense voltage changes across the cell membrane and open and close in response. The communication between voltage sensing and channel pore opening is known as electro-mechanical coupling, a process involving conformational changes of the protein during voltage-dependent activation.