TASK-1 (TWIK-related acid-sensitive potassium channel 1) and TASK-3 (TWIK-related acid-sensitive potassium channel 3) (TASK-1 and TASK-3)

TASK-1 (TWIK-related acid-sensitive potassium channel 1, KCNK3) and TASK-3 (TWIK-related acid-sensitive potassium channel 3, KCNK9) are members of the two-pore domain (K2P) potassium channel family. These channels generate background K+ currents that are crucial for establishing the resting membrane potential and regulating cellular excitability in neurons, cardiomyocytes, and other tissues. Both TASK-1 and TASK-3 are highly sensitive to extracellular pH (inhibited by acidification), and their activity can be modulated by GPCR signaling and other allosteric mechanisms. Structurally, they form dimeric channels with a unique "X-gate" controlling channel opening and closing, and their dysfunction—caused by genetic mutations or pharmacological modulation—is linked to human diseases such as sleep apnea, pain disorders, atrial fibrillation, and syndromic neurodevelopmental disorders. Both channels are considered promising drug targets for cardiovascular, respiratory, and neurological conditions.

Other names

KCNK3K2P3.1KCNK9K2P9.1TASK channelsK2P channelstwo-pore domain potassium channels

Channel inhibition (blocking K+ efflux, leading to depolarization) Channel activation (increasing K+ efflux, leading to hyperpolarization) Modulation by pH: acidification inhibits both channels Allosteric gating, including pH-dependent inhibition and C-type inactivation