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

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Target not currently curated in GtoImmuPdb

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

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
RefSeq Nucleotide
RefSeq Protein
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
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

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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
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
Species:  Mouse
Technique:  In situ hybridisation, RT-PCR
References:  7
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).


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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 et al.. (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 et al.. (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]


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