Potassium channel subfamily K member 9 (KCNK9) (TASK-3)

Potassium channel subfamily K member 9 (TASK-3) is a pH-sensitive, two-pore domain potassium (K2P) channel that plays a vital role in setting the resting membrane potential and controlling neuronal excitability (UniProt Q9NPC2). It is highly expressed in the central nervous system, particularly within the brainstem's serotonergic neurons of the dorsal raphe nucleus, where it modulates the firing patterns of these cells (PMID: 10801917). TASK-3 channels are sensitive to extracellular acidification, which leads to channel closure and subsequent neuronal depolarization (PMID: 21123634). This mechanism is crucial for physiological processes such as the respiratory response to CO2 and the regulation of sleep-wake cycles. Pathologically, mutations in the KCNK9 gene cause Birk-Barel syndrome, a genomic imprinting disorder, and the channel is frequently overexpressed in various malignancies, promoting tumor cell survival and proliferation (PMID: 25635015). Therapeutic strategies targeting TASK-3 include small-molecule inhibitors like doxapram for respiratory disorders and potential activators for neuroprotection. Because of its role in serotonergic signaling, it is also a target of interest for treating mood disorders and sleep-related breathing issues.

Other names

KCNK9TASK-3TASK3K2P9.1Acid-sensitive potassium channel protein 3

Modulation of background potassium leak current to regulate membrane potential and cellular excitability.