TASK-1 potassium channel, TASK-3 potassium channel (TASK-1 (KCNK3), TASK-3 (KCNK9))

TASK-1 and TASK-3 potassium channels are members of the two-pore domain (K2P) potassium channel family, encoded by the genes KCNK3 and KCNK9, respectively[3][4]. They are pH-sensitive background channels that regulate the resting membrane potential in excitable and non-excitable cells, such as neurons, cardiac myocytes, and endocrine cells[3][4]. TASK-1 and TASK-3 form potassium-selective pores and can heterodimerize with related channels such as TASK-5[5]. They play crucial roles in the regulation of aldosterone secretion, neuronal oscillations, sleep behavior, vascular tone, and pulmonary artery function[1][2][3][4]. Dysregulation or mutations in these channels are linked to pulmonary hypertension, neurodevelopmental disorders (including Birk-Barel syndrome), and cardiovascular diseases[3][4]. Pharmacologically, they are sensitive to extracellular pH, volatile anesthetics (e.g., halothane), and specific small-molecule modulators, making them valuable therapeutic targets[2][3][4][5]. Safety concerns relate to their wide physiological roles and risks of unintentionally inducing diseases by incorrect modulation[3][4][5].

Other names

TASK-1: TWIK-related acid-sensitive potassium channel 1, KCNK3TASK-3: TWIK-related acid-sensitive potassium channel 3, KCNK9

Positive allosteric modulation (activation of potassium currents) - Inhibition or activation by extracellular protons (pH-dependent gating) - Inhibitors reduce potassium efflux, increase depolarization - Activators increase potassium efflux, stabilize membrane potential