K<SUB>v</SUB>12.1 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv12.1

Target id: 575

Nomenclature: Kv12.1

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

   GtoImmuPdb view: OFF :     Currently no data for Kv12.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1107 3p24.3 KCNH8 potassium voltage-gated channel subfamily H member 8
Mouse 6 1 1102 17 C Kcnh8 potassium voltage-gated channel, subfamily H (eag-related), member 8
Rat 6 1 1102 9q11 Kcnh8 potassium voltage-gated channel subfamily H member 8
Previous and Unofficial Names
elk1 | elk3 | ELK channel 3 | ether-a-go-go-like potassium channel 1 | ether-a-go-go-like potassium channel 3 | Ets-1 | potassium voltage-gated channel, subfamily H (eag-related), member 8 | potassium channel, voltage gated eag related subfamily H, member 8 | potassium voltage-gated channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Ion Selectivity and Conductance
Species:  Human
Macroscopic current rectification:  Ik
References:  5
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -62.0 259.0 – 45.0 5 Xenopus laevis Oocytes Human
Inactivation  - -
Deactivation  - 331.0 – 66.0 5
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  9.0 - 2 Xenopus laevis Oocytes Rat
Inactivation  - -
Comments  Voltage sensitivity is sensitive to internal pH:
V0.5=10mV at pH 7.7

V0.5=28mV at pH 6.6
[2]
Associated subunits (Human)
minK (KCNE1)

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Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Zn2+ Mm - - - - - 4
[4]
Description: 1 mM Zn2+ slows activation 10-fold and shifts V0.5 for activation by ~+47 mV
Conditions: Heterologous expression in Xenopus oocytes
Cd2+ Mm - - - - - 4
[4]
Description: 1 mM Cd2+ slows activation 5-fold and shifts V0.5 for activation by +35 mV
Conditions: Heterologous expression in Xenopus oocytes
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+ Hs - 3.7 pIC50 - - 5
pIC50 3.7 [5]
Tissue Distribution
Primarily expressed in nervous system, especially prominent in the forebrain, cerebral cortex, hippocampus, amygdala, caudate, and nucleus accumbens. KCNH8 and KCNH3 genes also expressed together in the thalamus, substantia nigra, pons, and cerebellum; however the balance of expression level is shifted toward KCNH8. Expression very low in nonneuronal tissues.
Species:  Human
Technique:  RT-PCR
References:  5
Caudate / putamen, accumbens nuclei > cerebral cortex
Species:  Rat
Technique:  In situ hybridisation
References:  1
Functional Assays
Voltage clamp of heterologously expressed Kv12.1 currents
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  K+-selective channel, co-assembly with Kv12.2 and Kv12.3
References:  5
Voltage clamp of heterologously expressed Kv12.1 currents
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  Slowly activating outward rectifier
References:  2
Physiological Consequences of Altering Gene Expression
β-catenin regulates gene expression
Species:  Rat
Tissue:  Thalamic neurons
Technique: 
References:  3
General Comments
This channel has:
  • GFG (rather than the common GYG) potassium channel signature sequence
  • a PAS domain in the distal part of the cytosolic N-terminus
  • a cNBD domain in the proximal portion of the C-terminus

References

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1. Saganich MJ, Machado E, Rudy B. (2001) Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. J. Neurosci., 21 (13): 4609-24. [PMID:11425889]

2. Shi W, Wang HS, Pan Z, Wymore RS, Cohen IS, McKinnon D, Dixon JE. (1998) Cloning of a mammalian elk potassium channel gene and EAG mRNA distribution in rat sympathetic ganglia. J. Physiol. (Lond.), 511 ( Pt 3): 675-82. [PMID:9714851]

3. Wisniewska MB, Nagalski A, Dabrowski M, Misztal K, Kuznicki J. (2012) Novel β-catenin target genes identified in thalamic neurons encode modulators of neuronal excitability. BMC Genomics, 13: 635. [PMID:23157480]

4. Zhang X, Bursulaya B, Lee CC, Chen B, Pivaroff K, Jegla T. (2009) Divalent cations slow activation of EAG family K+ channels through direct binding to S4. Biophys. J., 97 (1): 110-20. [PMID:19580749]

5. Zou A, Lin Z, Humble M, Creech CD, Wagoner PK, Krafte D, Jegla TJ, Wickenden AD. (2003) Distribution and functional properties of human KCNH8 (Elk1) potassium channels. Am. J. Physiol., Cell Physiol., 285 (6): C1356-66. [PMID:12890647]

Contributors

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How to cite this page

Michael C. Sanguinetti, K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv12.1. Last modified on 07/10/2014. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=575.