Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels

Abstract

Neuronal KCNQ voltage-gated potassium channels mediate the muscarine-regulated M-current, which contributes to maintaining the resting membrane potential and is a key regulator in preventing hyperexcitability in neurons. Mutations within KCNQ2 alter channel function and result in devastating diseases such as benign familial neonatal seizures (BFNS) and epileptic encephalopathies, conditions that currently affect 50 million people worldwide. The impact that mutations have on channel function remain poorly defined, largely because of our limited understanding of the voltage sensing mechanisms that trigger channel gating.