Potassium channel subfamily K member 3

UniProt O14649 Organism Homo sapiens Gene KCNK3, TASK, TASK1

Also known as: KCNK3, TASK, TASK1

Function

K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Changes ion selectivity and becomes permeable to Na(+) ions in response to extracellular acidification. Protonation of the pH sensor His-98 stabilizes C-type inactivation conformation likely converting the channel from outward K(+)-conducting, to inward Na(+)-conducting to nonconductive state. Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. Allows K(+) currents with fast-gating kinetics important for the repolarization and hyperpolarization phases of action potentials (By similarity). In cerebellar granule cells, heteromeric KCNK3:KCNK9 channel may hyperpolarize the resting membrane potential to limit intrinsic neuronal excitability, but once the action potential threshold is reached, it may support high-frequency action potential firing and increased neuronal excitability (By similarity). Dispensable for central chemosensory respiration i.e. breathing controlled by brainstem CO2/pH, it rather conducts pH-sensitive currents and controls the firing rate of serotonergic raphe neurons involved in potentiation of the respiratory chemoreflex. Additionally, imparts chemosensitivity to type 1 cells in carotid bodies which respond to a decrease in arterial oxygen pressure or an increase in carbon dioxide pressure or pH to initiate adaptive changes in pulmonary ventilation (By similarity). In adrenal gland, contributes to the maintenance of a hyperpolarized resting membrane potential of aldosterone-producing cells at zona glomerulosa and limits aldosterone release as part of a regulatory mechanism that controls arterial blood pressure and electrolyte homeostasis (By similarity). In brown adipocytes, mediates K(+) efflux that counteracts norepinephrine-induced membrane depolarization, limits Ca(2+) efflux and downstream cAMP and PKA signaling, ultimately attenuating lipid oxidation and adaptive thermogenesis (By similarity).

Classification

Family (Pfam): PF07885 Ion_trans_2
InterPro: 2pore_dom_K_chnl, 2pore_dom_K_chnl_TASK, K_chnl_dom, KCNK3
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 4

6RV2 X-ray 3.00A
6RV3 X-ray 2.90A
6RV4 X-ray 3.10A
9G9X EM 3.13A

A predicted model is available from AlphaFold.

Gene Ontology · 24

Disease associations

pulmonary hypertension, primary, 4 MONDO:0014136
developmental delay with sleep apnea MONDO:0980728

Drugs targeting this protein · 6

SEVOFLURANE opener
DESFLURANE opener
ISOFLURANE opener
ENFLURANE opener
DOXAPRAM HYDROCHLORIDE blocker
HALOTHANE opener

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Potassium channel subfamily K member 3 2 shared papers
Potassium channel subfamily K member 15 1 shared papers
Potassium channel subfamily K member 9 3 shared papers
Potassium channel subfamily K member 1 2 shared papers
Potassium channel subfamily K member 2 2 shared papers
Potassium channel subfamily K member 4 1 shared papers
Potassium channel subfamily K member 1 1 shared papers
Potassium channel subfamily K member 2 1 shared papers
Potassium channel subfamily K member 17 1 shared papers
Potassium channel subfamily K member 5 1 shared papers
Potassium channel subfamily K member 4 1 shared papers
Potassium channel subfamily K member 10 1 shared papers

Literature · 11 cited papers

Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea. Nat. Genet. · 2022
A lower X-gate in TASK channels traps inhibitors within the vestibule. Nature · 2020
A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels. Cell · 2016
A novel channelopathy in pulmonary arterial hypertension. N. Engl. J. Med. · 2013
SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci. Signal. · 2012
Acid-sensitive TWIK and TASK two-pore domain potassium channels change ion selectivity and become permeable to sodium in extracellular acidification. J. Biol. Chem. · 2012
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
TASK-5, a novel member of the tandem pore K+ channel family. Pflugers Arch. · 2001
Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J. Biol. Chem. · 2000
Inhalational anesthetics activate two-pore-domain background K+ channels. Nat. Neurosci. · 1999
TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J. · 1997

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.