Kv6.4
Description: potassium voltage-gated channel, subfamily G, member 4 Gene: Kcng4 Synonyms: Kv6.4, kcng4
Kv6.4 is a potassium voltage-gated channel, subfamily G, member 4, also known as KV6.4; MGC4558; MGC129609. The electrically silent Kv channel α-subunit Kv6.4 is not capable of forming functional homotetrameric channels; however, it can heterotetramerize with Kv2.1 α-subunits to form functional Kv2.1/Kv6.4 channel complexes, presumably in a 3[ratio]1 stoichiometry [1838]. The gene has strong expression in brain. Multiple alternatively spliced variants have been found in normal and cancerous tissues.
http://www.ncbi.nlm.nih.gov/gene/93107
Experimental data
Rat Kv6.4 gene in CHO host cell datasheet |
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Mouse Kv6.4 gene in CHO host cell
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Human Kv6.4 gene in CHO host cell
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Gene
Transcript
Acc No | Sequence | Length | Source | |
---|---|---|---|---|
NM_001107435 | n/A | n/A | NCBI | |
NM_025734 | n/A | n/A | NCBI | |
NM_172347 | n/A | n/A | NCBI |
Ontology
Accession | Name | Definition | Evidence | |||||||
---|---|---|---|---|---|---|---|---|---|---|
GO:0008076 | voltage-gated potassium channel complex | A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. | IEA | |||||||
GO:0016020 | membrane | Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. | IEA |
Interaction
Aspartates in the T1 domain are required for efficient assembly of both homotetrameric Kv2.1 and heterotetrameric Kv2.1/silent Kv6.4 channels. [677]
Protein
Distribution
Expression
Domains Required for Kv6.4 Function
It has been demonstrated that Kv2.1 chimeras containing either S1 or S5 from Kv6.4 were functional, wheras a chimeric Kv2.1 subunit containing both the Kv6.4 S1 and S5 segments did not form functional channels. However, back mutation of some residues in this S1/S5 chimera restored functionality, and it was shown that interactions between S1, S4, and S5 are important for the functionality of WT Kv2.1 (4). It is possible that the inability to form electrically functional channels in homotetrameric configuration is due to the lack of such S1/S4/S5 interactions, at least in the case of Kv6.4 [1840]
His-105 in the T1 domain of Kv2.1 is required for functional heteromerization with members of the Kv6 subfamily, such as Kv6.4. [664]
Migraine
Several genes encoding potassium channels, including KCNK18, KCNG4, and KCNAB3, were identified as potentially linked to migraine [1839]
Human Kv6.4 Kinetics with Rat Kv2.1 in HEK293 Cells
Kv6.4 exerts several changes in the biophysical properties of Kv2.1 in Kv2.1/Kv6.4 channel complexes: a decrease in the current density [14] and a hyperpolarizing shift in the voltage-dependence of inactivation by ~40 mV, but without any significant effects on voltage-dependence of channel activation [15]. Here we show the modulating effects of Kv6.4 on Kv2.1 gating properties by analyzing the voltage-dependence of VSD movements in Kv2.1 and Kv2.1/Kv6.4 channels from IQ recordings. Our results suggest that Kv6.4 subunits display an intrinsic voltage-dependency with an operational VSD in heterotetrameric Kv2.1/Kv6.4 channels, by virtue of which it specifically influences the voltage-dependent inactivation properties of Kv2.1 [1838]
Kv6.4 with Kv2.1 in HEK293 Cells
Human Kv constructs were cloned in the mammalian vector peGFP-N1 (Clontech, Palo Alto, CA, USA). The Kv6.4 construct in which the C-terminus was exchanged for that of Kv3.1 as well as the N- and C-terminal segment constructs were constructed by PCR amplification using the QuickChange Site-Directed Mutagenesis kit (Stratagene La Jolla, CA, USA) and mutant primers. The main biophysical effect of WT Kv6.4 in a functional Kv2.1/Kv6.4 heterotetrameric channel is the approximately 40 mV hyperpolarizing shift in the voltage dependence of inactivation compared to Kv2.1 homotetramers. Indeed, the midpoint of inactivation for homotetrameric Kv2.1 currents was −23 mV which was shifted to −59 mV in heterotetrameric Kv2.1/Kv6.4 channels [1841]
Markov Model for Kv2.1/Kv6.4 Channel Gating
For convenience we used a simplified gating model (A) with a single transition between closed (C) and activated (A) state for each subunit, followed by the concerted step into the open (O) state (after all four subunits have reached the A-state). The equivalent Markov state-model (B) was built such that it could simulate both the heterotetrameric Kv2.1/Kv6.4 channel configuration with a 3[ratio]1 stoichiometry, as well as the homotetrameric Kv2.1 channel. To represent the heterotetrameric stoichiometry the closed and activated state of the Kv6.4 subunit are indicated with asterisks (C and A, respectively) [1838]
References
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et al.
Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels.
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606
Gutman GA
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International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.
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678
Kobertz WR
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Nat. Struct. Biol.,
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674
Tu L
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Voltage-gated K+ channels contain multiple intersubunit association sites.
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679
Zerangue N
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An artificial tetramerization domain restores efficient assembly of functional Shaker channels lacking T1.
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2000
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28
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599
Shen NV
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Molecular recognition and assembly sequences involved in the subfamily-specific assembly of voltage-gated K+ channel subunit proteins.
Neuron,
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, 14 (625-33).
660
Xu J
et al.
Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.
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680
Lee TE
et al.
Structural determinant for assembly of mammalian K+ channels.
Biophys. J.,
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681
Kobertz WR
et al.
Hanging gondola structure of the T1 domain in a voltage-gated K(+) channel.
Biochemistry,
2000
Aug
29
, 39 (10347-52).
Mederos Y Schnitzler M
et al.
Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
J. Biol. Chem.,
2009
Feb
13
, 284 (4695-704).
665
Rudy B
Diversity and ubiquity of K channels.
Neuroscience,
1988
Jun
, 25 (729-49).
Bocksteins E
et al.
The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.
PLoS ONE,
2012
, 7 (e37143).
Lafrenière RG
et al.
Identification of novel genes involved in migraine.
Headache,
2012
Oct
, 52 Suppl 2 (107-10).
Bocksteins E
et al.
Electrically silent Kv subunits: their molecular and functional characteristics.
Physiology (Bethesda),
2012
Apr
, 27 (73-84).
Bocksteins E
et al.
The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined by interactions between the N- and C-termini.
PLoS ONE,
2014
, 9 (e98960).
Credits
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/ionchannels/22/ , accessed on [date]