K<sub>ir</sub>5.1 | Inwardly rectifying potassium channels | IUPHAR Guide to IMMUNOPHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 440

Nomenclature: Kir5.1

Family: Inwardly rectifying potassium channels

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

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 418 17q23.1-24.2 KCNJ16 potassium inwardly rectifying channel subfamily J member 16 3,10
Mouse 2 1 419 11 E2 Kcnj16 potassium inwardly-rectifying channel 12
Rat 2 1 419 10q32.1 Kcnj16 potassium inwardly-rectifying channel 1,20
Previous and Unofficial Names
potassium inwardly rectifying channel subfamily J member 16 | BIR9 | inward rectifier K(+) channel Kir5.1 | inward rectifier potassium channel 16 | potassium channel, inwardly rectifying subfamily J, member 16 | potassium inwardly-rectifying channel | potassium voltage-gated channel subfamily J member 16
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir4.1 14
Kir4.2 14
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PSD-95 18
Functional Characteristics
Weakly inwardly rectifying
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+
References:  18
Ion Selectivity and Conductance Comments
Kir5.1 reported to form functional homomeric channels when expressed with PSD-95 [18].

Functional channels are also formed by heteromers of Kir5.1 with
· Kir4.1 (K+,43 pS, [15]
· Kir4.2 (K+, 54 pS, [14])

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

Gating Inhibitor Comments
PKA phosphorylation reported to inhibit activation of the Kir5.1/PSD-95 channel [18].

PKC phosphorylation reported to inhibit heteromeric Kir4.1/Kir5.1 channels [16].
Na+ influences PIP2 gating of heteromeric Kir4.1/Kir5.1 channels [17].
Intracellular H+ inhibits heteromeric Kir4.1/Kir5.1 channels [14,18,20].

Formation of heteromers with Kir5.1:
-Increases the sensitivity to intracellular pH (Kir4.1/5.1 pKi 7.1 vs. Kir4.1 6.0; Kir4.2/5.1 pKi 7.6 vs Kir4.2 pKi 7.6) [14]
-Imparts upregulation by intracellular Na+ [17]
-Reduces upregulation by extracellular K+ [4]
-Imparts sensitivity to inhibition by glutathione and oxidative stress [8].
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Ba2+ Rn Antagonist - - 3x10-3 -120.0 – 20.0 18
Conc range: 3x10-3 M Kir5.1 expressed with PSD-95 [18]
Holding voltage: -120.0 – 20.0 mV
Cs+ Rn Antagonist - - - Physiological 1
Holding voltage: Physiological
Tissue Distribution
Kidney (convoluted tubule cells), pancreas (acinar and ductal cells), thyroid gland.
Species:  Human
Technique:  In situ hybridisation
References:  10
Kidney (thick ascending limb of Henle’s loiop, distal convoluted tubule, cortical collecting duct basolateral membranes). These findings were also seen in rats
Species:  Mouse
Technique:  Electrophysiology, Immunohistochemistry
References:  9,11,20
Astrocytes (forebrain, olfactory bulb).
Species:  Mouse
Technique:  Immunohistochemistry
References:  5
Retina (Müller cells, GABAergic amacrine cells).
Species:  Rat
Technique:  Immunohistochemistry
References:  7
Brainstem nuclei (mesencephalic trigeminal, hypoglossal nucleus, facial, lateral reticular, para-ambiguus, paragigantocellularis, pontine), locus coeruleus, superior and inferior colliculi.
Species:  Rat
Technique:  In situ hybridisation
References:  3,21
Spleen, adrenal gland, liver, testis
Species:  Rat
Technique:  Northern Blot
References:  1
Carotid body (glomus cells, petrosukl ganglion)
Species:  Rat
Technique:  Immunohistochemistry
References:  22
Cochlea (spiral ligament of the lateral wall).
Species:  Rat
Technique:  Immunohistochemistry
References:  6
Physiological Functions
pH sensing
Species:  Rat
Tissue:  Kidney, brain, carotid body. Also demonstrated in mice.
References:  2,9,13,19-20,22


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1. Bond CT, Pessia M, Xia XM, Lagrutta A, Kavanaugh MP, Adelman JP. (1994) Cloning and expression of a family of inward rectifier potassium channels. Recept. Channels, 2 (3): 183-91. [PMID:7874445]

2. D'Adamo MC, Shang L, Imbrici P, Brown SD, Pessia M, Tucker SJ. (2011) Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity. J. Biol. Chem., 286 (1): 192-8. [PMID:21047793]

3. Derst C, Karschin C, Wischmeyer E, Hirsch JR, Preisig-Müller R, Rajan S, Engel H, Grzeschik K, Daut J, Karschin A. (2001) Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits. FEBS Lett., 491 (3): 305-11. [PMID:11240146]

4. Edvinsson JM, Shah AJ, Palmer LG. (2011) Potassium-dependent activation of Kir4.2 K⁺ channels. J. Physiol. (Lond.), 589 (Pt 24): 5949-63. [PMID:22025665]

5. Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y. (2004) Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. J. Biol. Chem., 279 (42): 44065-73. [PMID:15310750]

6. Hibino H, Higashi-Shingai K, Fujita A, Iwai K, Ishii M, Kurachi Y. (2004) Expression of an inwardly rectifying K+ channel, Kir5.1, in specific types of fibrocytes in the cochlear lateral wall suggests its functional importance in the establishment of endocochlear potential. Eur. J. Neurosci., 19 (1): 76-84. [PMID:14750965]

7. Ishii M, Fujita A, Iwai K, Kusaka S, Higashi K, Inanobe A, Hibino H, Kurachi Y. (2003) Differential expression and distribution of Kir5.1 and Kir4.1 inwardly rectifying K+ channels in retina. Am. J. Physiol., Cell Physiol., 285 (2): C260-7. [PMID:12686518]

8. Jin X, Yu L, Wu Y, Zhang S, Shi Z, Chen X, Yang Y, Zhang X, Jiang C. (2012) S-Glutathionylation underscores the modulation of the heteromeric Kir4.1-Kir5.1 channel in oxidative stress. J. Physiol. (Lond.), 590 (Pt 21): 5335-48. [PMID:22907060]

9. Lachheb S, Cluzeaud F, Bens M, Genete M, Hibino H, Lourdel S, Kurachi Y, Vandewalle A, Teulon J, Paulais M. (2008) Kir4.1/Kir5.1 channel forms the major K+ channel in the basolateral membrane of mouse renal collecting duct principal cells. Am. J. Physiol. Renal Physiol., 294 (6): F1398-407. [PMID:18367659]

10. Liu Y, McKenna E, Figueroa DJ, Blevins R, Austin CP, Bennett PB, Swanson R. (2000) The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas. Cytogenet. Cell Genet., 90 (1-2): 60-3. [PMID:11060447]

11. Lourdel S, Paulais M, Cluzeaud F, Bens M, Tanemoto M, Kurachi Y, Vandewalle A, Teulon J. (2002) An inward rectifier K(+) channel at the basolateral membrane of the mouse distal convoluted tubule: similarities with Kir4-Kir5.1 heteromeric channels. J. Physiol. (Lond.), 538 (Pt 2): 391-404. [PMID:11790808]

12. Mouri T, Kittaka N, Horio Y, Copeland NG, Gilbert DJ, Jenkins NA, Kurachi Y. (1998) Assignment of mouse inwardly rectifying potassium channel Kcnj16 to the distal region of mouse chromosome 11. Genomics, 54 (1): 181-2. [PMID:9806850]

13. Paulais M, Bloch-Faure M, Picard N, Jacques T, Ramakrishnan SK, Keck M, Sohet F, Eladari D, Houillier P, Lourdel S et al.. (2011) Renal phenotype in mice lacking the Kir5.1 (Kcnj16) K+ channel subunit contrasts with that observed in SeSAME/EAST syndrome. Proc. Natl. Acad. Sci. U.S.A., 108 (25): 10361-6. [PMID:21633011]

14. Pessia M, Imbrici P, D'Adamo MC, Salvatore L, Tucker SJ. (2001) Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1. J. Physiol. (Lond.), 532 (Pt 2): 359-67. [PMID:11306656]

15. Pessia M, Tucker SJ, Lee K, Bond CT, Adelman JP. (1996) Subunit positional effects revealed by novel heteromeric inwardly rectifying K+ channels. EMBO J., 15 (12): 2980-7. [PMID:8670799]

16. Rojas A, Cui N, Su J, Yang L, Muhumuza JP, Jiang C. (2007) Protein kinase C dependent inhibition of the heteromeric Kir4.1-Kir5.1 channel. Biochim. Biophys. Acta, 1768 (9): 2030-42. [PMID:17585871]

17. Rosenhouse-Dantsker A, Sui JL, Zhao Q, Rusinova R, Rodríguez-Menchaca AA, Zhang Z, Logothetis DE. (2008) A sodium-mediated structural switch that controls the sensitivity of Kir channels to PtdIns(4,5)P(2). Nat. Chem. Biol., 4 (10): 624-31. [PMID:18794864]

18. Tanemoto M, Fujita A, Higashi K, Kurachi Y. (2002) PSD-95 mediates formation of a functional homomeric Kir5.1 channel in the brain. Neuron, 34 (3): 387-97. [PMID:11988170]

19. Trapp S, Tucker SJ, Gourine AV. (2011) Respiratory responses to hypercapnia and hypoxia in mice with genetic ablation of Kir5.1 (Kcnj16). Exp. Physiol., 96 (4): 451-9. [PMID:21239463]

20. Tucker SJ, Imbrici P, Salvatore L, D'Adamo MC, Pessia M. (2000) pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia. J. Biol. Chem., 275 (22): 16404-7. [PMID:10764726]

21. Wu J, Xu H, Shen W, Jiang C. (2004) Expression and coexpression of CO2-sensitive Kir channels in brainstem neurons of rats. J. Membr. Biol., 197 (3): 179-91. [PMID:15042349]

22. Yamamoto Y, Ishikawa R, Omoe K, Taniguchi K. (2008) Expression of inwardly rectifying K+ channels in the carotid body of rat. Histol. Histopathol., 23 (7): 799-806. [PMID:18437678]


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