Kv11.3
Description: potassium voltage-gated channel, subfamily H (eag-related), member 7 Gene: Kcnh7 Alias: Kv11.3, erg3, kcnh7, HERG3
Kv11.3, encoded by the gene KCNH7 , is a voltage-activated potassium channel belonging to the eag family.
Experimental data
Rat Kv11.3 gene in CHO host cells datasheet |
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Gene
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_033272.4 | 4262 | |
Mouse | NM_133207.2 | 3798 | |
Rat | NM_131912.1 | 3807 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Visual Representation of Kv11.3 Structure
Methodology for visual representation of structure available here
The ether-a-go-go gene K+ channel alpha-subunits consist of six membrane-spanning domains (S1–S6). A Per-Arnt-Sim (PAS) domain is located at the N-terminus and a cyclic nucleotide-binding domain (cNBD) in the C-terminus. This, and the tetrameric structure of a K+ channel can be seen in fig1 of Bauer [778]. The pore region P and S6 may form the inner core of the channel, S1–S5 the outer parts of the channel with S4 as the voltage sensor. [778]
Kv11.3 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Human Kv11.3 inactivation in X oocytes
It can be seen from these data that the appearance of a transient waveform at positive potentials in the erg3 currents, but not the erg1 and erg2 currents, is attributable to differences in the relative rates of activation and inactivation. The ratio between the inactivation and activation rates of theerg3 channel was close to two at positive potentials, whereas inactivation rates were at least 10-fold faster than activation rates for both the erg1 and erg2 channels in this potential range. For the erg1 and erg2 channels, the inactivation process is in quasi-steady-state relative to the much slower activation process. The transient waveform of theerg3 current is produced by much the same mechanism as for a typical “A current,” which has an inactivation rate that is similar or somewhat slower than the activation rate. The primary difference between the erg3 current and a typical A current is the persistence of a maintained plateau current, which is attributable to the very shallow steady-state inactivation curve of the erg3 channel [790]
As expected, hKv11.3 inactivation was considerably slower than hKv11.1 and hKv11.2, which display similar inactivation rate [796].
Rat Herg3 (rKv11.3) expressed in CHO cells
NS1643 is one of the small molecule HERG (Kv11.1) channel activators and has also been found to increase erg2 (Kv11.2) currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3) channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV [1797]
Herg3 Expression in the Brain in Rats
HERG2 and HERG3 are expressed exclusively in brain [1743] All three Kv11 channels are expressed in the olfactory bulb, and erg1 and erg3 are co-expressed in the reticular thalamic nucleus, cerebral cortex, cerebellum and hippocampus [327]. Single cell RT-PCR experiments have shown that the erg subunits can be expressed in different combinations in individual rat lactotroph cells [781]. In addition, transcripts for more than one erg subunit have been detected in various cell lines: NG108-15 (neuroblastoma, erg1–3, [793]), PC12 (sympathetic ganglia neuron, erg1 and erg2, [327]), MMQ (lactotroph, erg1–3, [794]) and GH3/B6 (somatomammotroph, erg1 and erg2, [789]).
Kv11.2 and Kv11.3 are thought, contrary to Kv11.1, to be found exclusively in the nervous system [790]. However Kv11.2 and Kv11.3 transcripts were shown in rat pancreatic islets [798]. In rodent brain, the three channel subtypes display a widespread expression pattern [799], [326], [327]. although one study [327] did detect Kv11.2 almost exclusively in the olfactory bulb. (From [796])
The erg3 gene is broadly expressed throughout the nervous system, similar to erg1. In addition to brain,erg3 mRNA is expressed in all of the sympathetic ganglia tested and also is expressed at low levels in retina [790]
Association of Kv11.3 with bipolar spectrum disorders
Several mutations of Kv11.3 potassium channels were associated with the pathophysiology of bipolar spectrum disorders, particularly with bipolar 1 disorder, in genome-wide association studies. [2089] [2090]
BeKm-1 and APETx1
The toxins BeKm-1 and APETx1 reduced the currents mediated by erg1a and erg1a/erg3 concatemers to a similar degree as the erg current of Purkinje cells. A–D, BeKm-1 (100 nM) or APETx1 (1 μM) were applied to HEK 293 cells stably expressing erg1a, erg2, erg3, or concatemeric erg1a/erg3 channels.
References
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et al.
Biophysical properties of heteromultimeric erg K+ channels.
Pflugers Arch.,
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Expression pattern of the ether-a-gogo-related (ERG) K+ channel-encoding genes ERG1, ERG2, and ERG3 in the adult rat central nervous system.
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A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs.
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RERG is a molecular correlate of the inward-rectifying K current in clonal rat pituitary cells.
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Identification of two nervous system-specific members of the erg potassium channel gene family.
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Wimmers S
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Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers.
Pflugers Arch.,
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Meves H
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Separation of M-like current and ERG current in NG108-15 cells.
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Lecchi M
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Isolation of a long-lasting eag-related gene-type K+ current in MMQ lactotrophs and its accommodating role during slow firing and prolactin release.
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Functional properties of human neuronal Kv11 channels.
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A novel role for HERG K+ channels: spike-frequency adaptation.
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Circadian changes of ether-a-go-go-related-gene (Erg) potassium channel transcripts in the rat pancreas and beta-cell.
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Guasti L
et al.
Expression pattern of the ether-a-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits.
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Cordeiro S
et al.
Expression pattern of Kv11 (Ether à-go-go-related gene; erg) K+ channels in the mouse retina.
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Niculescu D
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Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation.
J. Neurosci.,
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Polvani S
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Developmentally regulated expression of the mouse homologues of the potassium channel encoding genes m-erg1, m-erg2 and m-erg3.
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et al.
Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.
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A population-based study of KCNH7 p.Arg394His and bipolar spectrum disorder.
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et al.
Identification of novel loci for bipolar I disorder in a multi-stage genome-wide association study.
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Contributors: Katherine Johnston
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