Function
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
Gene References into Functions
- mutations cause a gainoffunction of KV4.3/KChIP2encoded channels by increasing membrane protein expression and slowing channel inactivation. PMID: 26016905
- Mefloquine is a concentration-dependent Ito and hKv4.3 channel blocker. PMID: 26216464
- Altered Kv4.3 channel localization and/or functioning resulting from SCA19/22 mutations may lead to Purkinje cell loss, neurodegeneration and ataxia. PMID: 25854634
- the interaction of DPP10a, expressed in human atrium, with Kv4.3 channels generates a sustained current component of Ito, which may affect late repolarization phase of atrial action potentials. PMID: 25600224
- Kv4.3 K(+) channel is involved in heart hypertrophy/heart failure independently of its electric function.[review] PMID: 24762397
- Demonstrate SEMA3A as a naturally occurring protein that selectively inhibits Kv4.3 and SEMA3A as a possible Brugada syndrome susceptibility gene through a Kv4.3 gain-of-function mechanism. PMID: 24963029
- maps to chromosome 1p21-q21 and identification in Dutch autosomal dominant cerebellar ataxia family PMID: 12384780
- These results indicate that Kv4.3 is likely the target of discrepin and highlight the importance of the basic residue K13, located in the alpha-helix of the toxin, for current blockage. PMID: 24845726
- findings indicate mutations in KCND3 are not a common cause of disease among rarer types of European cerebellar ataxia; however 2 variants were identified in the SCA cases: p.L450F and p.P614S; mutations in KCND3 can cause 2 allelic disorders, SCA19/22 and Brugada syndrome which may co-occur PMID: 23963749
- Report a KV4.3 gain-of-function mutation in early-onset persistent lone atrial fibrillation. PMID: 23400760
- expression of the sodium (SCN5A) and potassium (KCND3) channels as well as the fibrosis content in the ventricles of heart failure and of non-diseased hearts under different post-mortem intervals PMID: 23036686
- The biophysical characteristics of Kv4.3 channels are strongly dependent on temperature. PMID: 23291429
- This study demonistrated that Mutations in KCND3 cause spinocerebellar ataxia type 22 in chinese and japanese. PMID: 23280837
- This study demonistrated that KCND3 mutations cause SCA19 by impaired protein maturation and/or reduced channel function PMID: 23280838
- KCND3 may serve as a rare genetic substrate in the pathogenesis of autopsy-negative sudden unexplained death (SUD) but not sudden infant death syndrome (SIDS) cases. PMID: 22457051
- Human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue. PMID: 22198508
- Deep insights into the mechanism of the regulation of Kv4.3 K channels and the role of Kv4.3 K channels in cell death. PMID: 22023388
- Kv4.3 macromolecular complex and regulators of KCND3 expression is needed to elucidate the role of the Ito current in the pathogenesis of BrS and other J-wave syndromes. PMID: 21349352
- The "structurally minimal" isoform KChIP2d modulates recovery of K(v)4.3 N-terminal deletion mutant Delta2-39. PMID: 21422811
- our findings suggest that KChIP1 interacts with Kv4.3 in interneurons at the stratum lacunosum-moleculare/radiatum junction PMID: 21129448
- The I(to) activator NS5806 modified Kv4.3/KChIP2 gating in several ways that inhibit current. PMID: 20649599
- KChIP4a functions to promote tetrameric assembly and enhance surface expression of Kv4 channels. PMID: 20550899
- N-linked glycosylation of DPP10 plays an important role in modulating Kv4.3 channel/KCHIP2 complex activities. PMID: 20354865
- Down-regulated atrial KChIP2 and Kv4.3 mRNA expressions in rheumatic heart disease patients with chronic atrial fibrillation might be one of the molecular bases responsible for the down-regulation of the I(to) current density of AF. PMID: 19927631
- Kv4.3 promiscuously assembles with ancillary subunits in vitro, functionally modifying the encoded currents. PMID: 12297301
- Analysis with chimeric proteins between KChIP2 and NCS-1 reveals that the three regions of KChIP2 are necessary and sufficient for its effective binding to Kv4.3 protein PMID: 12928444
- the two arginines in the cytosolic C-terminal domain of alpha-subunits of Kv4 subfamily strongly regulate the voltage dependence of channel activation, inactivation, and recovery PMID: 14645239
- Both Kv4.3 and KChIP2 may contribute to epicardial-endocardial gradients in the transient outward current in normal and failing hearts. PMID: 15498806
- Co-expression of SGK1, but not of SGK2 or SGK3, increased Kv 4.3/KChIP2b channel currents. PMID: 15578212
- Co-expression of DPPX in addition to Kv4.3 and KChIP2a produced similar current kinetics as in human ventricular myocytes PMID: 15890703
- KCNE3 also inhibits currents generated by Kv4.3 in complex with the accessory subunit KChIP2 PMID: 16782062
- the mechanisms involved in Syn1A-K(v) interactions vary significantly between K(v) channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability PMID: 17506992
- Kv4.3 regulates angiotensin type 1 receptor signaling to the small G-protein Rap-1 PMID: 17725712
- KCND3 mutations were not found to directly cause long QT syndrome. PMID: 18052691
- c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex PMID: 18620005
- NO and NO donors inhibited I(Kv4.3) in a concentration- and voltage-dependent manner. PMID: 18678642
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Involvement in disease
Spinocerebellar ataxia 19 (SCA19); Brugada syndrome 9 (BRGDA9)
Subcellular Location
Cell membrane; Multi-pass membrane protein. Cell membrane, sarcolemma; Multi-pass membrane protein. Cell projection, dendrite.
Protein Families
Potassium channel family, D (Shal) (TC 1.A.1.2) subfamily, Kv4.3/KCND3 sub-subfamily
Tissue Specificity
Highly expressed in heart and brain, in particular in cortex, cerebellum, amygdala and caudate nucleus. Detected at lower levels in liver, skeletal muscle, kidney and pancreas. Isoform 1 predominates in most tissues. Isoform 1 and isoform 2 are detected a