K<SUB>v</SUB>2.2 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 547

Nomenclature: Kv2.2

Family: Voltage-gated 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 6 1 911 8q13.2 KCNB2 potassium voltage-gated channel subfamily B member 2 19
Mouse 6 1 907 1 A3 Kcnb2 potassium voltage gated channel, Shab-related subfamily, member 2
Rat 6 1 907 5q11 Kcnb2 potassium voltage-gated channel subfamily B member 2
Previous and Unofficial Names
CDRK | potassium voltage-gated channel subfamily B member 2 | potassium voltage-gated channel, Shab-related subfamily, member 2 | potassium channel, voltage gated Shab related subfamily B, member 2 | potassium channel, voltage gated Shab-related subfamily B, member 2 | potassium voltage gated channel
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kv8.1 17
Kv9.1 18
Kv2.1 1,13
Kv9.2 18
Auxiliary Subunits
Name References
Kvβ4 5
Other Associated Proteins
Name References
KChaP 21
Ion Selectivity and Conductance
Species:  Dog
Rank order:  K+ [15.0 pS]
References:  19
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - 97.0 19 Xenopus laevis oocyte Dog
Inactivation  - -
Comments  A slowly activating K+ current, non-inactivating
Associated subunits (Human)
Kv5.1, Kv6.1-6.4, Kv8.1-8.2 and Kv9.1-9.3

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

Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
GxTx-1E Hs - 8.6 pKd - - 9
pKd 8.6 (Kd 2.6x10-9 M) [9]
ScTx1 Rn - 7.7 pIC50 - - 4
pIC50 7.7 (IC50 2.14x10-8 M) [4]
RY796 Hs - 7.1 pIC50 - - 8
pIC50 7.1 (IC50 9x10-8 M) [8]
View species-specific gating inhibitor tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
quinine Hs - 4.9 pIC50 - - 19
pIC50 4.9 [19]
fampridine Hs - 2.8 pIC50 - - 19
pIC50 2.8 (IC50 1.5x10-3 M) [19]
tetraethylammonium Hs - 2.6 pIC50 - - 19
pIC50 2.6 (IC50 2.6x10-3 M) [19]
Channel Blocker Comments
Phencyclidine (PCP) also inhbits human Kv2.2 from human colonic circular smooth muscle (pIC50 roughly 4.3) [6]
Tissue Distribution
Gastric cancer cells
Species:  Human
Technique:  RT-PCR
References:  14
Pancreatic islet delta cells
Species:  Human
Technique:  Immunohistochemistry
References:  23
Brain: neocortical neurons with partial overlap with Kv2.1, basal forebrain, medial nucleus of the trapezoid body
Species:  Mouse
Technique:  Immunohistochemistry
References:  7,12
Gastrointestinal smooth muscle, mesenteric artery smooth muscle
Species:  Rat
Technique:  RT-PCR
References:  22
Brain neocortical neurons with partial overlap with Kv2.1, basal forebrain, medial nucleus of the trapezoid body
Species:  Rat
Technique:  Immunohistochemistry
References:  7,13
Tissue Distribution Comments
Also: Rabbit myocytes from corpus cavernosum (RT-PCR, [16]), Ferret cardiac myocytes (In situ hybridisation, [3]).
Functional Assays
Gene cloning and voltage clamp
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  slowly activating K+ current
References:  19
Physiological Functions
Maintaining membrane potential, modulating electrical excitability in neurons
Species:  Rat
Tissue:  Superior cervical ganglion (SCG)
References:  15
Maintaining membrane potential, modulating electrical excitability in spinal chord neurons
Species:  None
Tissue:  Xenopus laevis spinal chord neurons
References:  2
Maintain high frequency action potential firing
Species:  Mouse
Tissue:  MNTB neurons
References:  12
Physiological Functions Comments
Species ([2]): Xenopus laevis embryonic spinal neurons
Gene Expression and Pathophysiology
KV2.2 expression in DRG neurons decreased after peripheral axotomy.
Tissue or cell type:  Dorsal root ganglion neurones
Pathophysiology:  Repetitive firing and peripheral hyperexcitability
Species:  Rat
Technique:  In situ hybridisation
References:  20
Biologically Significant Variant Comments
A total of 7585 SNPs have been identified in human KCNB2. For more information, please see the entry on GeneCards.
General Comments
The angiotensin II type 1 receptor mediates inhibition of Kv2.2 in the brainstem and hypothalamic neurons. It is a member of the mammalian Shab-related family. Some immunohistochemical studies performed with antibodies that were generated against an incorrect sequence of rat Kv2.2 [10], some studies on recombinant Kv2.2 channels using the rat cDNA may be confounded by incorrect sequence, as published in [11]. See [13] for correction.


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1. Blaine JT, Ribera AB. (1998) Heteromultimeric potassium channels formed by members of the Kv2 subfamily. J. Neurosci., 18 (23): 9585-93. [PMID:9822719]

2. Blaine JT, Taylor AD, Ribera AB. (2004) Carboxyl tail region of the Kv2.2 subunit mediates novel developmental regulation of channel density. J. Neurophysiol., 92 (6): 3446-54. [PMID:15306626]

3. Brahmajothi MV, Morales MJ, Liu S, Rasmusson RL, Campbell DL, Strauss HC. (1996) In situ hybridization reveals extensive diversity of K+ channel mRNA in isolated ferret cardiac myocytes. Circ. Res., 78 (6): 1083-9. [PMID:8635239]

4. Escoubas P, Diochot S, Célérier ML, Nakajima T, Lazdunski M. (2002) Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol. Pharmacol., 62 (1): 48-57. [PMID:12065754]

5. Fink M, Duprat F, Lesage F, Heurteaux C, Romey G, Barhanin J, Lazdunski M. (1996) A new K+ channel beta subunit to specifically enhance Kv2.2 (CDRK) expression. J. Biol. Chem., 271 (42): 26341-8. [PMID:8824288]

6. Frey BW, Lynch FT, Kinsella JM, Horowitz B, Sanders KM, Carl A. (2000) Blocking of cloned and native delayed rectifier K channels from visceral smooth muscles by phencyclidine. Neurogastroenterol. Motil., 12 (6): 509-16. [PMID:11123705]

7. Hermanstyne TO, Kihira Y, Misono K, Deitchler A, Yanagawa Y, Misonou H. (2010) Immunolocalization of the voltage-gated potassium channel Kv2.2 in GABAergic neurons in the basal forebrain of rats and mice. J. Comp. Neurol., 518 (21): 4298-310. [PMID:20853508]

8. Herrington J, Solly K, Ratliff KS, Li N, Zhou YP, Howard A, Kiss L, Garcia ML, McManus OB, Deng Q et al.. (2011) Identification of novel and selective Kv2 channel inhibitors. Mol. Pharmacol., 80 (6): 959-64. [PMID:21948463]

9. Herrington J, Zhou YP, Bugianesi RM, Dulski PM, Feng Y, Warren VA, Smith MM, Kohler MG, Garsky VM, Sanchez M et al.. (2006) Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion. Diabetes, 55 (4): 1034-42. [PMID:16567526]

10. Hwang PM, Fotuhi M, Bredt DS, Cunningham AM, Snyder SH. (1993) Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily. J. Neurosci., 13 (4): 1569-76. [PMID:8463836]

11. Hwang PM, Glatt CE, Bredt DS, Yellen G, Snyder SH. (1992) A novel K+ channel with unique localizations in mammalian brain: molecular cloning and characterization. Neuron, 8 (3): 473-81. [PMID:1550672]

12. Johnston J, Griffin SJ, Baker C, Skrzypiec A, Chernova T, Forsythe ID. (2008) Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons. J. Physiol. (Lond.), 586 (14): 3493-509. [PMID:18511484]

13. Kihira Y, Hermanstyne TO, Misonou H. (2010) Formation of heteromeric Kv2 channels in mammalian brain neurons. J. Biol. Chem., 285 (20): 15048-55. [PMID:20202934]

14. Lan M, Shi Y, Han Z, Hao Z, Pan Y, Liu N, Guo C, Hong L, Wang J, Qiao T et al.. (2005) Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells. Cancer Biol. Ther., 4 (12): 1342-7. [PMID:16258262]

15. Malin SA, Nerbonne JM. (2002) Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons. J. Neurosci., 22 (23): 10094-105. [PMID:12451110]

16. Malysz J, Farrugia G, Ou Y, Szurszewski JH, Nehra A, Gibbons SJ. (2002) The Kv2.2 alpha subunit contributes to delayed rectifier K(+) currents in myocytes from rabbit corpus cavernosum. J. Androl., 23 (6): 899-910. [PMID:12399537]

17. Salinas M, de Weille J, Guillemare E, Lazdunski M, Hugnot JP. (1997) Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J. Biol. Chem., 272 (13): 8774-80. [PMID:9079713]

18. Salinas M, Duprat F, Heurteaux C, Hugnot JP, Lazdunski M. (1997) New modulatory alpha subunits for mammalian Shab K+ channels. J. Biol. Chem., 272 (39): 24371-9. [PMID:9305895]

19. Schmalz F, Kinsella J, Koh SD, Vogalis F, Schneider A, Flynn ER, Kenyon JL, Horowitz B. (1998) Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles. Am. J. Physiol., 274 (5 Pt 1): G901-11. [PMID:9612272]

20. Tsantoulas C, Zhu L, Yip P, Grist J, Michael GJ, McMahon SB. (2014) Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input. Exp. Neurol., 251: 115-26. [PMID:24252178]

21. Wible BA, Yang Q, Kuryshev YA, Accili EA, Brown AM. (1998) Cloning and expression of a novel K+ channel regulatory protein, KChAP. J. Biol. Chem., 273 (19): 11745-51. [PMID:9565597]

22. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am. J. Physiol., 277 (5): G1055-63. [PMID:10564112]

23. Yan L, Figueroa DJ, Austin CP, Liu Y, Bugianesi RM, Slaughter RS, Kaczorowski GJ, Kohler MG. (2004) Expression of voltage-gated potassium channels in human and rhesus pancreatic islets. Diabetes, 53 (3): 597-607. [PMID:14988243]


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