K<sub>2P</sub>5.1 | Two P domain potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

K2P5.1

Target id: 517

Nomenclature: K2P5.1

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 K2P5.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 499 6q21 KCNK5 potassium two pore domain channel subfamily K member 5 8
Mouse 4 2 502 14 Kcnk5 potassium channel, subfamily K, member 5
Rat 4 2 503 15p16 Kcnk5 potassium two pore domain channel subfamily K member 5
Previous and Unofficial Names
TASK-2 | potassium channel subfamily K member 5 | potassium channel, two pore domain subfamily K, member 5 | potassium channel
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
Interaction with G protein β subunits 1 and 2 reported in vitro [1].
Functional Characteristics
Background current

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 Hs - 3.7 pIC50 1x10-4 - 1x10-3 - 4
pIC50 3.7 Conc range: 1x10-4 - 1x10-3 M [4]
Activator Comments
Volatile anesthetics appear to activate the human tandem pore domain baseline K+ channel K2P5.1 [4].
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
clofilium Mm - 4.6 pIC50 - - 7
pIC50 4.6 [7]
quinidine Hs - - - - - 5
[5]
View species-specific channel blocker tables
Channel Blocker Comments
K2P5.1 is sensitive to (blocked by) external pH is seen over a wide pHo range of 6-10. The effect of pH changes is mainly on the opening frequency [5].
Tissue Distribution
Brain
Expression level:  High
Species:  Rat
Technique:  Immunohistochemistry
References:  3
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnk5+|Kcnk5Gt(KST024)Byg|Phox2b+|Phox2btm2Jbr Kcnk5Gt(KST024)Byg/Kcnk5+,Phox2btm2Jbr/Phox2b+
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
MGI:1100882  MGI:1336175  MP:0005277 abnormal brainstem morphology PMID: 20133877 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0005556 abnormal kidney clearance PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0005555 abnormal kidney excretion PMID: 15141089 
Kcnk5Gt(KST024)Byg Kcnk5Gt(KST024)Byg/Kcnk5Gt(KST024)Byg
B6.129P2-Kcnk5
MGI:1336175  MP:0003633 abnormal nervous system physiology PMID: 20133877 
Kcnk5Gt(KST024)Byg Kcnk5Gt(KST024)Byg/Kcnk5Gt(KST024)Byg
B6.129P2-Kcnk5
MGI:1336175  MP:0001943 abnormal respiration PMID: 20133877 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0001262 decreased body weight PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0006275 natriuresis PMID: 15141089 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
involves: 129P2/OlaHsd * C57BL/6J
MGI:1336175  MP:0002080 prenatal lethality PMID: 12707131 
Kcnk5Gt(pGT1.8TM)1Gray Kcnk5Gt(pGT1.8TM)1Gray/Kcnk5Gt(pGT1.8TM)1Gray
B6.129P2-Kcnk5
MGI:1336175  MP:0002080 prenatal lethality PMID: 15141089 
General Comments
A role in cell volume regulation [2,7] and sensing external basolateral pH changes associated HCO3- transport primary cultured proximal tubular cells [9]. ‘Activation’ and ‘deactivation’ with voltage steps appear instantaneous. The conductance of K2P5 is dependent on the ionic conditions. The slope conductance was reported as 15 pS with 5 mM external potassium and as high as 60 pS when external potassium is high (155 mM) 1. This may reflect a Na+ dependent inward rectification which becomes progressively less pronounced with time [6]. Like K2P16 and 17 current through K2P5 channels is diminished at physiological pH. Channel open probability increases with external pH. Formation of an inter-subunit disulfide bridge in K2P5 does not affect channel activity. Exposure to hypotonicity (change from 300 to 200 mOsm in external solution) enhanced mK2P5 currents when this channel was heterologously expressed in HEK293 cells and osmotic cell shrinkage led to inhibition (change from 300 to 400 mOsm in external solution).

References

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1. Añazco C, Peña-Münzenmayer G, Araya C, Cid LP, Sepúlveda FV, Niemeyer MI. (2013) G protein modulation of K2P potassium channel TASK-2 : a role of basic residues in the C terminus domain. Pflugers Arch., 465 (12): 1715-26. [PMID:23812165]

2. Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J, Poujeol P. (2003) Role of TASK2 potassium channels regarding volume regulation in primary cultures of mouse proximal tubules. J. Gen. Physiol., 122 (2): 177-90. [PMID:12860925]

3. Gabriel A, Abdallah M, Yost CS, Winegar BD, Kindler CH. (2002) Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Brain Res. Mol. Brain Res., 98 (1-2): 153-63. [PMID:11834308]

4. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CS. (2000) Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5. Anesthesiology, 92 (6): 1722-30. [PMID:10839924]

5. Kang D, Kim D. (2004) Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem. Biophys. Res. Commun., 315 (4): 836-44. [PMID:14985088]

6. Morton MJ, Chipperfield S, Abohamed A, Sivaprasadarao A, Hunter M. (2005) Na(+)-induced inward rectification in the two-pore domain K(+) channel, TASK-2. Am. J. Physiol. Renal Physiol., 288 (1): F162-9. [PMID:15328068]

7. Niemeyer MI, Cid LP, Barros LF, Sepúlveda FV. (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J. Biol. Chem., 276 (46): 43166-74. [PMID:11560934]

8. Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M. (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J. Biol. Chem., 273 (47): 30863-9. [PMID:9812978]

9. Warth R, Barrière H, Meneton P, Bloch M, Thomas J, Tauc M, Heitzmann D, Romeo E, Verrey F, Mengual R, Guy N, Bendahhou S, Lesage F, Poujeol P, Barhanin J. (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proc. Natl. Acad. Sci. U.S.A., 101 (21): 8215-20. [PMID:15141089]

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: K2P5.1. Last modified on 09/03/2017. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=517.