K<sub>ir</sub>4.2 | Inwardly rectifying potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kir4.2

Target id: 439

Nomenclature: Kir4.2

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

   GtoImmuPdb view: OFF :     Currently no data for Kir4.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 375 21q22.2 KCNJ15 potassium voltage-gated channel subfamily J member 15 9
Mouse 2 1 402 16 C4 Kcnj15 potassium inwardly-rectifying channel, subfamily J, member 15 7
Rat 2 1 405 11q11 Kcnj15 potassium voltage-gated channel subfamily J member 15 2
Previous and Unofficial Names
IRKK | ATP-sensitive inward rectifier potassium channel 15 | inward rectifier K(+) channel Kir4.2 | Kir1.3 | potassium channel, inwardly rectifying subfamily J, member 15 | potassium inwardly-rectifying channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir5.1 7-8
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CIPP 4
CaS receptor 3
MUPP 10
Functional Characteristics
Inward-rectifier current
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+ [25.2 pS]
References:  8
Ion Selectivity and Conductance Comments
A functional channel is also formed by a Kir4.2/5.1 heteromer (K+, 54.2pS, [8]).
Voltage Dependence Comments
Kir4.2 forms channels that display moderate rectification: in low (2 mM) K+, currents are essentially ohmic below 0 mV, while in isomolar K+ rectification is strong, with little outward current above 0 mV [7].

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Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Extracellular K+ Mm Activation - - 1x10-1 -140.0 – 80.0 1,7
Conc range: 1x10-1 M [1,7]
Holding voltage: -140.0 – 80.0 mV
Activator Comments
In excised patches channels are constitutively active [8]. In Xenopus oocytes prolonged exposure to elevated extracellular K+ causes slow activation of whole cell current by an unknown mechanism [7].
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Intracellular H+ Rn Antagonist 6.7 – 7.1 pEC50 - -100.0 8
pEC50 6.7 – 7.1 [8]
Holding voltage: -100.0 mV
Gating Inhibitor Comments
Kir4.2/5.1 heteromers also form functional channels that are pH sensitive (pEC50=7.64, [8]). Endogenous inhibitors intracellular Mg2+ and polyamines (spermine4+, spermidine3+, putrescine2+), although voltage-dependence and sensitivity are not as strong as for Kir2 channels.
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Ba2+ Mm Antagonist - - 1x10-5 - 1x10-4 -120.0 – 100.0 7
Conc range: 1x10-5 - 1x10-4 M Kir4.2 expressed in Xenopus oocytes [7]
Holding voltage: -120.0 – 100.0 mV
Cs+ Mm Antagonist - - 1x10-5 - 1x10-4 -120.0 – 100.0 7
Conc range: 1x10-5 - 1x10-4 M Kir4.2 expressed in Xenopus oocytes [7]
Holding voltage: -120.0 – 100.0 mV
Tissue Distribution
Kidney, pancreas > lung > prostate, testes, leukocytes.
Species:  Human
Technique:  Northern Blot
References:  5,9
E12.5: Thymus and thyroid gland.
E14.5: Heart valves, thymus medulla, thyroid gland, perichondrium, epidermis.
E17.5: Head (maxillar and mandibular regions, olfactory epithelium, tongue, oropharynx and nasopharynx epithelium, submandibular and lacrimal glands, submandibular and sublingual ducts, teeth primordia, vibrissae, hair follicles), kidney (developing tubules), stomach, thymus, heart valves, lung, bladder, limbs (perichondrium, ligaments, tendons).
Species:  Mouse
Technique:  In situ hybridisation
References:  11
Hepatocyte basolateral membrane.
Species:  Rat
Technique:  Immunohistochemistry
References:  2
Functional Assays
Voltage clamp recording of cloned channel in heterologous expression systems.
Species:  Rat
Tissue:  HEK 293T cells.
Response measured:  Current.
References:  2
Voltage clamp recording of the cloned channel in heterologous expression systems.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Current.
References:  7-8
Clinically-Relevant Mutations and Pathophysiology
Disease:  Diabetes mellitus, noninsulin-dependent; NIDDM
Synonyms: Diabetes mellitus, Type II; T2D [OMIM: 125853]
Maturity onset diabetes
Type 2 diabetes mellitus [Disease Ontology: DOID:9352]
Disease Ontology: DOID:9352
OMIM: 125853
Comments: 
References:  6
Biologically Significant Variants
Type:  Splice variant
Species:  Mouse
Amino acids:  375
Nucleotide accession: 
Protein accession: 
References:  7
Type:  Splice variant
Species:  Mouse
Amino acids:  402
Nucleotide accession: 
Protein accession: 
General Comments
Mouse and rat Kir4.2 channel activity has been successfully studied in heterologous expression systems, while human Kir4.2 has not. Channels that may be comprised of human Kir4.2 have been recorded in Calu-3 cells, a model for human airway gland serous cells [12]. Proteins CIPP and CaR, reported as auxiliary subunits, were identified in yeast 2 hybrid screens [3-4]. No evidence of their interactions in native tissue has been reported to date. Likewise, interactions between Kir5.1 and Kir4.2 have been demonstrated electrophysiologically in heterologous expression systems [7-8], but interaction of these proteins in native tissue has not been demonstrated.

References

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1. 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]

2. Hill CE, Briggs MM, Liu J, Magtanong L. (2002) Cloning, expression, and localization of a rat hepatocyte inwardly rectifying potassium channel. Am. J. Physiol. Gastrointest. Liver Physiol., 282 (2): G233-40. [PMID:11804844]

3. Huang C, Sindic A, Hill CE, Hujer KM, Chan KW, Sassen M, Wu Z, Kurachi Y, Nielsen S, Romero MF, Miller RT. (2007) Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function. Am. J. Physiol. Renal Physiol., 292 (3): F1073-81. [PMID:17122384]

4. Kurschner C, Mermelstein PG, Holden WT, Surmeier DJ. (1998) CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins. Mol. Cell. Neurosci., 11 (3): 161-72. [PMID:9647694]

5. Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M. (1997) Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res., 7 (1): 47-58. [PMID:9037601]

6. Okamoto K, Iwasaki N, Doi K, Noiri E, Iwamoto Y, Uchigata Y, Fujita T, Tokunaga K. (2012) Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes. Diabetes, 61 (7): 1734-41. [PMID:22566534]

7. Pearson WL, Dourado M, Schreiber M, Salkoff L, Nichols CG. (1999) Expression of a functional Kir4 family inward rectifier K+ channel from a gene cloned from mouse liver. J. Physiol. (Lond.), 514 ( Pt 3): 639-53. [PMID:9882736]

8. 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]

9. Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, Bienkowski MJ. (1997) Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3). J. Biol. Chem., 272 (1): 586-93. [PMID:8995301]

10. Sindic A, Huang C, Chen AP, Ding Y, Miller-Little WA, Che D, Romero MF, Miller RT. (2009) MUPP1 complexes renal K+ channels to alter cell surface expression and whole cell currents. Am. J. Physiol. Renal Physiol., 297 (1): F36-45. [PMID:19420109]

11. Thiery E, Gosset P, Damotte D, Delezoide AL, de Saint-Sauveur N, Vayssettes C, Créau N. (2000) Developmentally regulated expression of the murine ortholog of the potassium channel KIR4.2 (KCNJ15). Mech. Dev., 95 (1-2): 313-6. [PMID:10906485]

12. Wu JV, Krouse ME, Rustagi A, Joo NS, Wine JJ. (2004) An inwardly rectifying potassium channel in apical membrane of Calu-3 cells. J. Biol. Chem., 279 (45): 46558-65. [PMID:15328350]

Contributors

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How to cite this page

Paul A. Slesinger, Colin G. Nichols, Lawrence G. Palmer, Henry Sackin, Stephen Tucker, John P. Adelman, David E. Clapham, Hiroshi Hibino, Atsushi Inanobe, Lily Y. Jan, Andreas Karschin, Yoshihiro Kubo, Yoshihisa Kurachi, Michel Lazdunski, Takashi Miki, Wade L. Pearson, Susumu Seino, Carol A. Vandenberg.
Inwardly rectifying potassium channels: Kir4.2. Last modified on 27/02/2018. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=439.