Potassium channel subfamily K member 3 (KCNK3) (TASK-1)

Potassium channel subfamily K member 3 (KCNK3), commonly known as TASK-1, is a member of the two-pore domain potassium (K2P) channel family that mediates background leak currents essential for setting the resting membrane potential (UniProt: P48524). It is primarily expressed in the heart, lungs, and central nervous system, where it regulates cellular excitability and responds to physiological stimuli such as extracellular pH and oxygen levels (PubMed: 10903571). In the cardiovascular system, TASK-1 is a key determinant of atrial repolarization and pulmonary vascular tone, making it a significant factor in the pathogenesis of atrial fibrillation and pulmonary arterial hypertension (PubMed: 31554101, 23644490). Pharmacological inhibition of TASK-1 is being explored as a strategy to treat rhythm disorders by prolonging the atrial refractory period, while its activation is investigated for reducing pulmonary resistance. Drugs such as doxapram and various experimental small molecules (e.g., BAY 2586116) interact with the channel's pore or sensing domains to modulate its activity (IUPHAR/BPS Guide to Pharmacology). Understanding TASK-1's role in chemoreception also highlights its potential as a target for respiratory conditions like sleep apnea (PubMed: 32810011).

Other names

K2P3.1TBAK-1Acid-sensitive potassium channel protein 1Two pore domain potassium channel TASK-1TWIK-related acid-sensitive K+ channel 1

TASK-1 modulators typically function as pore blockers (inhibitors) to increase cellular excitability and prolong action potential duration, or as activators to hyperpolarize the membrane and reduce excitability (IUPHAR/BPS Guide to Pharmacology).