Recombinant Rat Potassium voltage-gated channel subfamily A member 4 (Kcna4)

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Description

Molecular Identity and Production

Gene and Protein Structure

  • Gene: Kcna4 (synonyms: Kv4, RK3, RHK1, Kv1.4) encodes a 655-amino-acid protein with six transmembrane domains (S1–S6) and a pore-forming region between S5–S6 .

  • Isoforms: Full-length recombinant Kcna4 (1-655 aa) and partial constructs are available, with purity ≥85% by SDS-PAGE .

Expression Systems

Host SystemPurityApplicationsSource
E. coli≥85%Structural studies, ELISA
Mammalian cells≥85%Functional assays, WB
Cell-free systems≥85%High-throughput screening

Biological Functions and Mechanisms

Cardiac Electrophysiology

  • Kcna4 encodes the α-subunit of Kv1.4 channels, mediating slowly inactivating transient outward K⁺ currents (I<sub>to,s</sub>) during cardiac action potential repolarization .

  • Knockout mice (Kv1.4<sup>−/−</sup>) show reduced I<sub>to</sub> current density, prolonging action potential duration .

Transcriptional Regulation

  • Nucleoporin 50 (Nup50) binds the Kcna4 promoter via its FG-repeat domain, enhancing transcription and Kv1.4 protein expression in cardiomyocytes .

  • Overexpression of Nup50 increases I<sub>to,s</sub> current density by 77% (+70 mV; P<0.01) .

Neuronal Signaling

  • Kv1.4 channels associate with postsynaptic density protein 95 (PSD-95) in lipid rafts, modulating synaptic plasticity .

  • Cumulative inactivation properties (time constants: τ<sub>fast</sub> ≈ 200 ms; τ<sub>slow</sub> ≈ 2.5 s) influence neuronal firing patterns .

Key Research Findings

Table 1: Functional Insights from Experimental Models

Model SystemKey FindingMethodologiesSource
NRVMsNup50 depletion reduces Kv1.4 by 60%qRT-PCR, WB, ChIP
HEK293 cellsNup50 elevates KCNA4 mRNA 4-foldCRISPR/dCas9-VP64
Rat brain membranes30% of Kv1.4 partitions into lipid raftsSucrose gradient, WB
Xenopus oocytesKv1.4 shows cumulative inactivationVoltage-clamp

Research Applications

  • Antibody Validation: Anti-Kv1.4 monoclonal antibodies (e.g., K13/31, L71/5R) enable immunohistochemistry (IHC) and Western blotting .

  • Disease Modeling: Linked to microcephaly, cataracts, and dystonia in OMIM annotations .

  • Drug Development: Used to screen modulators of I<sub>to,s</sub> currents for arrhythmia therapies .

Clinical and Pathological Relevance

  • Ischemic heart tissues show correlated Nup50 and Kv1.4 downregulation, suggesting transcriptional dysregulation in cardiac pathologies .

  • Altered Kv1.4-PSD-95 interactions may contribute to neurological disorders via disrupted lipid raft signaling .

Product Specs

Form
Lyophilized powder
Note: While we prioritize shipping the format currently in stock, please specify your format preference in order remarks for customized preparation.
Lead Time
Delivery times vary depending on purchasing method and location. Consult your local distributor for precise delivery estimates.
Note: Standard shipping includes blue ice packs. Dry ice shipping requires advance notice and incurs additional charges.
Notes
Avoid repeated freeze-thaw cycles. Store working aliquots at 4°C for up to one week.
Reconstitution
Centrifuge the vial briefly before opening to settle the contents. Reconstitute the protein in sterile deionized water to a concentration of 0.1-1.0 mg/mL. For long-term storage, we recommend adding 5-50% glycerol (final concentration) and aliquoting at -20°C/-80°C. Our standard glycerol concentration is 50%, provided as a guideline.
Shelf Life
Shelf life depends on storage conditions, buffer composition, temperature, and protein stability. Generally, liquid formulations have a 6-month shelf life at -20°C/-80°C, while lyophilized forms have a 12-month shelf life at -20°C/-80°C.
Storage Condition
Upon receipt, store at -20°C/-80°C. Aliquot for multiple uses to prevent repeated freeze-thaw cycles.
Tag Info
The tag type is determined during manufacturing.
The tag type is determined during the production process. If you require a specific tag, please inform us for prioritized development.
Synonyms
Kcna4; Potassium voltage-gated channel subfamily A member 4; RCK4; RHK1; RK3; Voltage-gated potassium channel subunit Kv1.4
Buffer Before Lyophilization
Tris/PBS-based buffer, 6% Trehalose.
Datasheet
Please contact us to get it.
Expression Region
1-655
Protein Length
Full length protein
Species
Rattus norvegicus (Rat)
Target Names
Kcna4
Target Protein Sequence
MEVAMVSAESSGCNSHMPYGYAAQARARERERLAHSRAAAAAAVAAATAAVEGTGGSGGG PHHHHQTRGAYSSHDPQGSRGSREEEATRTEKKKKLHHRQSSFPHCSDLMPSGSEEKILR ELSEEEEDEEEEEEEEEEGRFYYSEEDHGDGCSYTDLLPQDDGGGGGYSSVRYSDCCERV VINVSGLRFETQMKTLAQFPETLLGDPEKRTQYFDPLRNEYFFDRNRPSFDAILYYYQSG GRLKRPVNVPFDIFTEEVKFYQLGEEALLKFREDEGFVREEEDRALPENEFKKQIWLLFE YPESSSPARGIAIVSVLVILISIVIFCLETLPEFRDDRDLIMALSAGGHSRLLNDTSAPH LENSGHTIFNDPFFIVETVCIVWFSFEFVVRCFACPSQALFFKNIMNIIDIVSILPYFIT LGTDLAQQQGGGNGQQQQAMSFAILRIIRLVRVFRIFKLSRHSKGLQILGHTLRASMREL GLLIFFLFIGVILFSSAVYFAEADEPTTHFQSIPDAFWWAVVTMTTVGYGDMKPITVGGK IVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETENEEQTQLTQNAVSCPYLPSNLLKKFR SSTSSSLGDKSEYLEMEEGVKESLCGKEEKCQGKGDDSETDKNNCSNAKAVETDV
Uniprot No.

Target Background

Function
Voltage-gated potassium channel mediating transmembrane potassium transport in excitable membranes. It forms tetrameric potassium-selective channels, facilitating potassium ion passage according to their electrochemical gradient. The channel undergoes voltage-dependent transitions between open and closed conformations. It can form functional homotetramers and heterotetramers with variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and potentially other family members; channel properties vary depending on the alpha subunit composition. Cytoplasmic beta subunits modulate channel properties by regulating alpha subunit subcellular localization and promoting rapid inactivation. In vivo, membranes likely contain a mixture of heteromeric potassium channel complexes, making it challenging to attribute currents in intact tissues to specific family members. Homotetrameric KCNA4 channels open upon membrane depolarization, followed by rapid spontaneous closure. Similarly, heterotetrameric channels (e.g., KCNA1/KCNA4) exhibit rapid inactivation.
Gene References Into Functions
  1. Four prolines and four lysines in a Kv1.4 homotetramer may constitute a binding site for a putative endoplasmic reticulum-export molecule, ensuring high cell surface protein expression. PMID: 28054303
  2. Synaptotagmin I interacts with the Kv1.4 channel. PMID: 24423395
  3. Intracellular free heme potently regulates Kv1.4 K(+) channels; heme binds to the N-terminal inactivation domain, impairing inactivation. PMID: 24082096
  4. Cystathionine-β-synthetase (endogenous H2S-generating enzyme) shows co-localization with Kv1.1 and Kv1.4 in trigeminal ganglion neurons. PMID: 23413915
  5. Immunocytochemistry reveals increased Kv1.4 protein expression between 1 and 4-5 weeks of age. PMID: 21451062
  6. N-type inactivation prevention (NIP) domain function requires Kv1.6 positioning adjacent to the Kv1.4 subunit. PMID: 21352098
  7. NMR assignments for the 48 kDa tetramer of the T1 domain of Kv1.4 (Kv1.4). PMID: 19888682
  8. Kv1.4 channels are widely distributed in the rat brain; their activation exerts diverse modulatory effects on neuronal excitability. PMID: 14615029
  9. Preventing N-glycosylation of Kv1.4 reduces protein stability, increases intracellular retention, and decreases cell surface protein levels. PMID: 14688283
  10. Kv3.4 subunit immunoreactivity (Kv3.4-IR) is widespread, with dense punctate staining in regions including the intermediolateral cell column (IML), dorsal vagal nucleus (DVN), nucleus ambiguus (NA), and nucleus tractus solitarius (NTS). PMID: 15207333
  11. Diffusible factors coordinate pregnancy-associated changes in the molecular composition of myometrial Kv4-KChIP channel complexes. PMID: 15454398
  12. Immunohistochemical co-expression of carbonic anhydrase II with Kv1.4 and TRPV1 in rat small-diameter trigeminal ganglion neurons. PMID: 15885224
  13. Neuronal transmission stimulation elevates Kv1.4 phosphorylation at Ser229 via Ca2+ influx through the NMDA receptor. PMID: 16000151
  14. Kv4α subunits encode IA channels; IA plays a crucial role in shaping action potential waveforms and controlling repetitive firing in visual cortical pyramidal neurons. PMID: 16207878
  15. Continuum electrostatics was used to investigate interactions between Kv1.4 mutants (H508 or K532) and K(+) sites in the pore. PMID: 17359997
  16. Temporomandibular joint (TMJ) inflammation reduces Kv1.4 subunit expression in small/medium-sized (Aδ-/C-) trigeminal ganglion neurons, potentially contributing to trigeminal inflammatory allodynia in TMJ disorders. PMID: 17584507
  17. Removing the fast N-type inactivation gate (Δ6-46) reveals steric interference of internal TEA with an internally located slow inactivation gate in a Xenopus oocytes expression system. PMID: 19029372
  18. Bladder inflammation increases bladder afferent neuron excitability by decreasing Kv1.4 α-subunit expression. PMID: 19279288
  19. Arachidonic acid and Trolox potently modulate Kv1.4 and Kv4.2 channel α-subunits, potentially tuning presynaptic transmitter release and postsynaptic somatodendritic excitability in synaptic transmission and plasticity. PMID: 19453640
Database Links

KEGG: rno:25469

STRING: 10116.ENSRNOP00000006524

UniGene: Rn.9884

Protein Families
Potassium channel family, A (Shaker) (TC 1.A.1.2) subfamily, Kv1.4/KCNA4 sub-subfamily
Subcellular Location
Cell membrane; Multi-pass membrane protein. Cell projection, axon.
Tissue Specificity
Detected in brain (at protein level). Heart and brain.

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