K<sub>2P</sub>3.1 | Two P domain potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

K2P3.1

Target id: 515

Nomenclature: K2P3.1

Family: Two P domain potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for K2P3.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 394 2p24.1-23.3 KCNK3 potassium two pore domain channel subfamily K member 3 15
Mouse 4 2 409 5 B Kcnk3 potassium channel, subfamily K, member 3 15
Rat 4 2 411 6q14 Kcnk3 potassium two pore domain channel subfamily K member 3 11
Previous and Unofficial Names
TASK-1 | OAT-1 | TWIK-related acid-sensitive K+ channel | two pore potassium channel KT3.1 | potassium channel, two pore domain subfamily K, member 3 | potassium channel
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
K2P9.1 1,6-7
K2P1.1 20
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
syntaxin-8 21
14-3-3 17
COP1 17
Vpu1 5
Associated Protein Comments
Heteromultimers shown to form in vivo: K2P3 has been shown to form heterodimers with K2P9 in rat cerebellar granule neurons [6], in rat carotid body glomus cells [7] and in motoneurons [1] and with K2P1 in rat cerebellar granule neurons [20].

Protein-protein interactions: K2P3 has been found to associate with syntaxin-8 [21]; 14-3-3 [17] and the coatomer coat protein 1 (COP1) [17] and Vpu1 [5]. Binding of 14-3-3 and COP1 control forward trafficking of K2P3 from the ER [17]. Forward trafficking is modulated by the binding of p11 to K2P3 in a 14-3-3 dependent manner [18]. The electrical activity of K2P3-K2P1 heterodimers at the plasma membrane is controlled by SUMOylation of the K2P1 subunit [20].
Functional Characteristics
Background current
Ion Selectivity and Conductance Comments
K2P3.1 or TASK-1 channels generate instantaneous, open-rectifier K+ currents (showing the Goldman-Hodgkin-Katz (GHK) rectifier behaviour) [11].

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
halothane Rn Positive 3.0 pEC50 1x10-3 - 19,23
pEC50 3.0 (EC50 1x10-3 M) Conc range: 1x10-3 M studied at 1-10 mM [19,23]
isoflurane Rn Positive 2.7 pEC50 - - 23
pEC50 2.7 [23]
halothane Hs - - - - -
studied at 1-10 mM
View species-specific activator tables
Activator Comments
Volatile anesthetics are known activators of the K2P3.1 channels [2,8,23].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
angiotensin II {Sp: Human, Mouse, Rat} Rn - - - 1x10-8 - 3
Conc range: 1x10-8 M [3]
anandamide Hs - ~6.2 pIC50 - - 14
pIC50 ~6.2 (IC50 ~7x10-7 M) [14]
R-(+)-methanandamide Hs - ~6.2 pIC50 - - 14
pIC50 ~6.2 (IC50 ~7x10-7 M) [14]
anandamide Hs Inhibition 5.6 pIC50 - - 14
pIC50 5.6 (IC50 2.7x10-6 M) [14]
arachidonic acid Hs - 1.0 pIC50 - 0.0 14
pIC50 1.0 [14]
Holding voltage: 0.0 mV
Ba2+ Hs - 0.3 pIC50 - -
pIC50 0.3
View species-specific channel blocker tables
Channel Blocker Comments
Proton block and voltage gating are potassium-dependent in K2P3.1. The channels are modulated by external pH [4,12-13].
Tissue Distribution
Cerebellar granule neurons
Species:  Mouse
Technique:  Immunocytochemistry, RT-PCR
References:  16
Heart.
Species:  Rat
Technique:  Northern Blot
References:  9
Lung, kidney.
Species:  Rat
Technique:  Northern Blot
References:  3
Tissue Distribution Comments
Other reports have suggested expression in pancreas, prostate, uterus and placenta.
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnk3tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100509  MP:0005402 abnormal action potential PMID: 18094244 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100509  MGI:3521816  MP:0005402 abnormal action potential PMID: 18094244 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0002909 abnormal adrenal gland physiology PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0003484 abnormal channel response PMID: 18250325 
Kcnk3tm1Sgb Kcnk3tm1Sgb/Kcnk3tm1Sgb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100509  MP:0001516 abnormal motor coordination/ balance PMID: 16339039 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0003353 decreased circulating renin level PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0005333 decreased heart rate PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0000231 hypertension PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0004119 hypokalemia PMID: 18250325 
Kcnk3tm1.1Daba|Kcnk9tm1.1Daba Kcnk3tm1.1Daba/Kcnk3tm1.1Daba,Kcnk9tm1.1Daba/Kcnk9tm1.1Daba
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1100509  MGI:3521816  MP:0002666 increased circulating aldosterone level PMID: 18250325 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Pulmonary hypertension, primary 4; PPH4
Synonyms: Heritable pulmonary arterial hypertension [Orphanet: ORPHA275777]
Idiopathic pulmonary arterial hypertension [Orphanet: ORPHA275766]
Primary pulmonary hypertension [Disease Ontology: DOID:14557]
Disease Ontology: DOID:14557
OMIM: 615344
Orphanet: ORPHA275777, ORPHA275766
General Comments
‘Activation’ and ‘deactivation’ with voltage steps appears to be instantaneous but there is also a small, time-dependent change in Po. Current is half-blocked at pH 7.3 at physiological external conditions; increasing external potassium decreases proton blockade. Pharmacology studies of the rat variant reveal blockade also by zinc, TEA and quinidine [10,22]. K2P3 like currents are reported in cerebellar granular neurons and motor-neurons [10,16]. Interaction with 14-3-3 protein is essential for forward trafficking. K2P3 can form heterodimers with K2P9.1 in heterologous expression systems consistent with electrophysiological studies that suggest heterodimerzation. K2P3 is also suggested to be a target for transmitter modulation of neuronal excitability [10,16].

References

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1. Berg AP, Talley EM, Manger JP, Bayliss DA. (2004) Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J. Neurosci., 24 (30): 6693-702. [PMID:15282272]

2. Buckler KJ, Williams BA, Honore E. (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J. Physiol. (Lond.), 525 Pt 1: 135-42. [PMID:10811732]

3. Czirják G, Fischer T, Spät A, Lesage F, Enyedi P. (2000) TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II. Mol. Endocrinol., 14 (6): 863-74. [PMID:10847588]

4. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J., 16 (17): 5464-71. [PMID:9312005]

5. Hsu K, Seharaseyon J, Dong P, Bour S, Marbán E. (2004) Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol. Cell, 14 (2): 259-67. [PMID:15099524]

6. Kang D, Han J, Talley EM, Bayliss DA, Kim D. (2004) Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J. Physiol. (Lond.), 554 (Pt 1): 64-77. [PMID:14678492]

7. Kim D, Cavanaugh EJ, Kim I, Carroll JL. (2009) Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J. Physiol. (Lond.), 587 (Pt 12): 2963-75. [PMID:19403596]

8. Kim D, Fujita A, Horio Y, Kurachi Y. (1998) Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ. Res., 82 (4): 513-8. [PMID:9506712]

9. Kim Y, Bang H, Kim D. (1999) TBAK-1 and TASK-1, two-pore K(+) channel subunits: kinetic properties and expression in rat heart. Am. J. Physiol., 277 (5 Pt 2): H1669-78. [PMID:10564119]

10. Kindler CH, Yost CS, Gray AT. (1999) Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. Anesthesiology, 90 (4): 1092-102. [PMID:10201682]

11. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, Chavez RA, Forsayeth JR, Yost CS. (1998) An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J. Neurosci., 18 (3): 868-77. [PMID:9437008]

12. Lopes CM, Gallagher PG, Buck ME, Butler MH, Goldstein SA. (2000) Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J. Biol. Chem., 275 (22): 16969-78. [PMID:10748056]

13. Lopes CM, Zilberberg N, Goldstein SA. (2001) Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers. J. Biol. Chem., 276 (27): 24449-52. [PMID:11358956]

14. Maingret F, Patel AJ, Lazdunski M, Honoré E. (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1. EMBO J., 20 (1-2): 47-54. [PMID:11226154]

15. Manjunath NA, Bray-Ward P, Goldstein SA, Gallagher PG. (1999) Assignment of the 2P domain, acid-sensitive potassium channel OAT1 gene KCNK3 to human chromosome bands 2p24.1-->p23.3 and murine 5B by in situ hybridization. Cytogenet. Cell Genet., 86 (3-4): 242-3. [PMID:10575216]

16. Millar JA, Barratt L, Southan AP, Page KM, Fyffe RE, Robertson B, Mathie A. (2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proc. Natl. Acad. Sci. U.S.A., 97 (7): 3614-8. [PMID:10725353]

17. O'Kelly I, Butler MH, Zilberberg N, Goldstein SA. (2002) Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell, 111 (4): 577-88. [PMID:12437930]

18. O'Kelly I, Goldstein SA. (2008) Forward Transport of K2p3.1: mediation by 14-3-3 and COPI, modulation by p11. Traffic, 9 (1): 72-8. [PMID:17908283]

19. Patel AJ, Honoré E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M. (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J., 17 (15): 4283-90. [PMID:9687497]

20. Plant LD, Zuniga L, Araki D, Marks JD, Goldstein SA. (2012) SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci Signal, 5 (251): ra84. [PMID:23169818]

21. Renigunta V, Fischer T, Zuzarte M, Kling S, Zou X, Siebert K, Limberg MM, Rinné S, Decher N, Schlichthörl G et al.. (2014) Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1. Mol. Biol. Cell, 25 (12): 1877-91. [PMID:24743596]

22. Talley EM, Lei Q, Sirois JE, Bayliss DA. (2000) TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron, 25 (2): 399-410. [PMID:10719894]

23. Washburn CP, Sirois JE, Talley EM, Guyenet PG, Bayliss DA. (2002) Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance. J. Neurosci., 22 (4): 1256-65. [PMID:11850453]

Contributors

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How to cite this page

Leigh D. Plant, Douglas A. Bayliss, Daniel L. Minor, Jr., Gábor Czirják, Péter Enyedi, Florian Lesage, Francisco Sepúlveda, Steve A.N. Goldstein.
Two P domain potassium channels: K2P3.1. Last modified on 09/03/2017. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=515.