Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) (Kv7.1)

The Kv7.1 channel, also known as KCNQ1, is a critical voltage-gated potassium channel primarily expressed in the heart, inner ear, and various epithelial tissues [2, 14]. In cardiac myocytes, it associates with the auxiliary subunit KCNE1 to form the complex responsible for the slow delayed rectifier potassium current (IKs), which is essential for terminating the action potential and maintaining a stable heart rhythm [4, 8]. Mutations in the KCNQ1 gene are the most common cause of inherited Long QT syndrome (LQT1), a condition that predisposes individuals to life-threatening arrhythmias and sudden death [9, 11]. In the inner ear, the channel is vital for maintaining the endolymph's ionic composition, and its dysfunction can lead to sensorineural deafness as seen in Jervell and Lange-Nielsen syndrome [2, 3]. Additionally, Kv7.1 plays a role in regulating insulin secretion in the pancreas and salt transport in the gastrointestinal tract and kidneys [12, 14]. Pharmacological modulation of Kv7.1 focuses on activators to treat repolarization disorders and inhibitors to investigate its diverse physiological roles across multiple organ systems [1, 20].

Other names

KCNQ1KvLQT1KQT-like 1Voltage-gated potassium channel subunit Kv7.1KCNA8KCNA9JLNS1LQT1SQT2ATFB1ATFB3IKs producing slow voltage-gated potassium channel subunit alpha

Drugs targeting the Kv7.1 channel act as either activators or inhibitors to modulate the potassium current [1, 20]. Activators, such as ML277, increase the channel's open probability or shift its voltage-dependent activation to more hyperpolarized potentials, thereby enhancing the IKs current and shortening the cardiac action potential [1, 14]. Conversely, inhibitors like HMR 1556 and Chromanol 293B block the pore or interfere with gating mechanisms, leading to a reduction in potassium efflux, which prolongs the action potential and can be used to study channel function or investigate its role in disease states [6, 8, 20].