Channelpedia

Kv11.3

Description: potassium voltage-gated channel, subfamily H (eag-related), member 7
Gene: Kcnh7
Alias: Kv11.3, erg3, kcnh7, HERG3

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Introduction

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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show 104 cells
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Gene

Species NCBI gene ID Chromosome Position
Human 90134 2 467360
Mouse 170738 2 490552
Rat 170739 3 492784
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Transcript

Species NCBI accession Length (nt)
Human NM_033272.4 4262
Mouse NM_133207.2 3798
Rat NM_131912.1 3807
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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q9NS40 1196
Mouse Q9ER47 1195
Rat O54852 1195

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform
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Post-Translational Modifications

PTM
Position
Type
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Structure

Kv11.3
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

Species Area (Å2) Reference
Human 7145.76 source
Mouse 7537.91 source
Rat 6771.59 source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Human Kv11.3 inactivation in X oocytes

Kv.11.1 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

Kv.11.1 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]

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Expression and Distribution

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]

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Function

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]

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Interaction

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

325

Wimmers S et al. Biophysical properties of heteromultimeric erg K+ channels.
Pflugers Arch., 2002 Dec , 445 (423-30).

327

Saganich MJ et al. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain.
J. Neurosci., 2001 Jul 1 , 21 (4609-24).

778

Bauer CK et al. Physiology of EAG K+ channels.
J. Membr. Biol., 2001 Jul 1 , 182 (1-15).

780

Akbarali HI et al. Role of HERG-like K(+) currents in opossum esophageal circular smooth muscle.
Am. J. Physiol., 1999 Dec , 277 (C1284-90).

781

Bauer CK et al. A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs.
Mol. Cell. Endocrinol., 1999 Feb 25 , 148 (37-45).

792

Wimmers S et al. Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers.
Pflugers Arch., 2001 Jan , 441 (450-5).

793

Meves H et al. Separation of M-like current and ERG current in NG108-15 cells.
Br. J. Pharmacol., 1999 Jul , 127 (1213-23).

796

Einarsen K et al. Functional properties of human neuronal Kv11 channels.
Pflugers Arch., 2009 Aug , 458 (689-700).

797

Chiesa N et al. A novel role for HERG K+ channels: spike-frequency adaptation.
J. Physiol. (Lond.), 1997 Jun 1 , 501 ( Pt 2) (313-8).

1797

Bilet A et al. Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.
PLoS ONE, 2012 , 7 (e50886).

2089

Strauss KA et al. A population-based study of KCNH7 p.Arg394His and bipolar spectrum disorder.
Hum. Mol. Genet., 2014 Dec 1 , 23 (6395-406).

2090

Kuo PH et al. Identification of novel loci for bipolar I disorder in a multi-stage genome-wide association study.
Prog. Neuropsychopharmacol. Biol. Psychiatry, 2014 Jun 3 , 51 (58-64).

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Credits

Contributors: Katherine Johnston

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/37/ , accessed on 2024 Dec 21


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