Potassium voltage-gated channel subfamily Q member 1 (KCNQ1) (KCNQ1)

The KCNQ1 potassium channel, also known as Kv7.1, is a voltage-gated ion channel critical for the repolarization of the cardiac action potential [2, 3, 5, 8]. It co-assembles with the auxiliary subunit KCNE1 to form the slow delayed rectifier potassium current (IKs), which regulates the duration of the action potential and maintains normal heart rhythm [12, 13, 16, 18]. Beyond the myocardium, KCNQ1 is expressed in various epithelial tissues, including the inner ear, where it maintains the endocochlear potential necessary for hearing, and the gastrointestinal tract, where it supports gastric acid secretion and ion homeostasis [1, 3, 7, 8, 11]. Pathogenic mutations in the KCNQ1 gene are primarily associated with Long QT syndrome type 1 (LQT1) and Jervell and Lange-Nielsen syndrome, disorders that significantly increase the risk of sudden cardiac death [2, 3, 5, 10, 16]. Pharmacologically, KCNQ1 is targeted by experimental activators such as ML277 and R-L3, which are being investigated for their potential to treat LQT1 by enhancing channel conductance [12, 13]. Conversely, unintended inhibition of KCNQ1 by various drugs is a major cause of acquired QT prolongation and associated pro-arrhythmic risks [4, 15].

Other names

Kv7.1KvLQT1KCNA8KCNA9JLNS1LQT1Potassium voltage-gated channel subfamily KQT member 1KQT-like 1IKs producing slow voltage-gated potassium channel alpha subunit

Drugs targeting KCNQ1 primarily act via two mechanisms: channel activation and channel inhibition. Activators (e.g., ML277, R-L3) enhance the potassium current by increasing channel conductance or shifting the voltage dependence of activation, which can shorten the action potential duration in conditions like LQT1 [12, 13]. Conversely, inhibitors (e.g., Chromanol 293B, HMR 1556, Quinidine) block the ion-permeating pore or allosterically inhibit the channel, reducing the repolarizing current and lengthening the action potential [4, 9].