K<SUB>v</SUB>4.1 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv4.1

Target id: 552

Nomenclature: Kv4.1

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 Kv4.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 647 Xp11.23 KCND1 potassium voltage-gated channel subfamily D member 1 9
Mouse 6 1 651 X A1.1 Kcnd1 potassium voltage-gated channel, Shal-related family, member 1 16
Rat 6 1 651 Xq13 Kcnd1 potassium voltage-gated channel subfamily D member 1 6
Previous and Unofficial Names
Potassium voltage-gated channel subfamily D member 1 | potassium channel, voltage gated Shal related subfamily D, member 1 | potassium channel, voltage gated Shal-related subfamily D, member 1 | potassium voltage-gated channel
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not shown to date
Auxiliary Subunits
Name References
DPP6, DPP10 10-11,14
KChIP1-4 1-2,15
Other Associated Proteins
Name References
Not determined
Functional Characteristics
KA
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [6.0 pS] > Na+ [0.06 pS] > Rb+ [- pS]
References:  1,12,18
Species:  Mouse
Macroscopic current rectification:  Transient, voltage-sensitive A-Type current
References:  12
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - Xenopus laevis oocyte Mouse
Inactivation  - 31.0 2-3
Comments  KChIP1 mainly impairs open-state inactivation, favours channel closing and lowers the energy barrier of closed-state inactivation.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -82.5 - 18 Xenopus laevis oocyte Mouse
Inactivation  - 300.0 3
Comments  Inside out patch.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -72.3 - 18 Xenopus laevis oocyte Mouse
Inactivation  - -70.0 3
Comments  Cell attached patch.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -47.9 - 12 Xenopus laevis oocyte Mouse
Inactivation  -69.0 22.0 12
Comments  Fast inactivating. Properties depend on the expression system and recording configuration.
Associated subunits (Human)
KChIP 1-4, DP66, DPP10

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

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
HmTx1 Mm - 6.5 pIC50 - - 5
pIC50 6.5 [5]
tetraethylammonium Hs - 2.0 pIC50 - - 13
pIC50 2.0 [13]
fampridine Hs - 2.0 pIC50 - - 9
pIC50 2.0 [9]
fampridine Mm - 2.0 pIC50 - - 8
pIC50 2.0 [8]
View species-specific channel blocker tables
Tissue Distribution
Brain, heart, liver, kidney, thyroid gland, pancreas.
Species:  Human
Technique:  Northern blot
References:  9
Heart
Species:  Mouse
Technique:  In situ hybridisation, RT-PCR
References:  7
Brain
Species:  Rat
Technique:  Northern blot
References:  17
Tissue Distribution Comments
Also: Ferret - Brain (fetal, infant and adult), colon, heart, lung, stomach, testis, liver, kidney, thyroid gland, pancreas, pulmonary artery [4]
Functional Assays
Inside-out patches
Species:  Mouse
Tissue:  Xenopus laevis oocytes
Response measured:  Transient, voltage-sensitive A-type K+ current
References:  1,3
Cloned subunit and two-electrode voltage-clamp
Species:  Mouse
Tissue:  Xenopus laevis oocytes
Response measured:  Transient, voltage-sensitive A-type K+ current
References:  16
RT-PCR, voltage clamp
Species:  Human
Tissue:  HEK-293 cells
Response measured:  Transient, voltage-sensitive A-type K+ current
References:  13
General Comments
It is a member of the mammalian Shal-related family.

The Kv4.1 (KCND1) gene is encoded by at least 6 exons: the first exon encodes the protein from the N-terminus through S5 into the P-region, whereas the remainder of the protein is encoded by exons 2 - 6.
The kinetic properties depend on the expression system, recording configuration, and the presence of auxiliary subunits (KChIPs).

References

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1. An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS et al.. (2000) Modulation of A-type potassium channels by a family of calcium sensors. Nature, 403 (6769): 553-6. [PMID:10676964]

2. Beck EJ, Bowlby M, An WF, Rhodes KJ, Covarrubias M. (2002) Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein. J. Physiol. (Lond.), 538 (Pt 3): 691-706. [PMID:11826158]

3. Beck EJ, Covarrubias M. (2001) Kv4 channels exhibit modulation of closed-state inactivation in inside-out patches. Biophys. J., 81 (2): 867-83. [PMID:11463631]

4. 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]

5. 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]

6. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol. Rev., 57 (4): 473-508. [PMID:16382104]

7. Harrell MD, Harbi S, Hoffman JF, Zavadil J, Coetzee WA. (2007) Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development. Physiol. Genomics, 28 (3): 273-83. [PMID:16985003]

8. Holmqvist MH, Cao J, Hernandez-Pineda R, Jacobson MD, Carroll KI, Sung MA, Betty M, Ge P, Gilbride KJ, Brown ME, Jurman ME, Lawson D, Silos-Santiago I, Xie Y, Covarrubias M, Rhodes KJ, Distefano PS, An WF. (2002) Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain. Proc. Natl. Acad. Sci. U.S.A., 99 (2): 1035-40. [PMID:11805342]

9. Isbrandt D, Leicher T, Waldschütz R, Zhu X, Luhmann U, Michel U, Sauter K, Pongs O. (2000) Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Genomics, 64 (2): 144-54. [PMID:10729221]

10. Jerng HH, Pfaffinger PJ, Covarrubias M. (2004) Molecular physiology and modulation of somatodendritic A-type potassium channels. Mol. Cell. Neurosci., 27 (4): 343-69. [PMID:15555915]

11. Jerng HH, Qian Y, Pfaffinger PJ. (2004) Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10). Biophys. J., 87 (4): 2380-96. [PMID:15454437]

12. Jerng HH, Shahidullah M, Covarrubias M. (1999) Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore. J. Gen. Physiol., 113 (5): 641-60. [PMID:10228180]

13. Jiang B, Sun X, Cao K, Wang R. (2002) Endogenous Kv channels in human embryonic kidney (HEK-293) cells. Mol. Cell. Biochem., 238 (1-2): 69-79. [PMID:12349911]

14. Nadal MS, Ozaita A, Amarillo Y, Vega-Saenz de Miera E, Ma Y, Mo W, Goldberg EM, Misumi Y, Ikehara Y, Neubert TA et al.. (2003) The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron, 37 (3): 449-61. [PMID:12575952]

15. Nakamura TY, Nandi S, Pountney DJ, Artman M, Rudy B, Coetzee WA. (2001) Different effects of the Ca(2+)-binding protein, KChIP1, on two Kv4 subfamily members, Kv4.1 and Kv4.2. FEBS Lett., 499 (3): 205-9. [PMID:11423117]

16. Pak MD, Baker K, Covarrubias M, Butler A, Ratcliffe A, Salkoff L. (1991) mShal, a subfamily of A-type K+ channel cloned from mammalian brain. Proc. Natl. Acad. Sci. U.S.A., 88 (10): 4386-90. [PMID:2034678]

17. Serôdio P, Rudy B. (1998) Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain. J. Neurophysiol., 79 (2): 1081-91. [PMID:9463463]

18. Shahidullah M, Covarrubias M. (2003) The link between ion permeation and inactivation gating of Kv4 potassium channels. Biophys. J., 84 (2 Pt 1): 928-41. [PMID:12547775]

Contributors

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How to cite this page

Jeanne Nerbonne, Bernardo Rudy, K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv4.1. Last modified on 15/09/2015. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=552.