Channelpedia

Kv9.3

Description: potassium voltage-gated channel, delayed-rectifier, subfamily S, member 3
Gene: Kcns3
Alias: Kv9.3, kcns3

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Introduction

Kv9.3 (also known as MGC9481), encoded by the gene HCNS3, is member 3 of subfamily S of delayed-rectifier potassium voltage-gated channels. Kv9.3 is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. NCBI

Experimental data

Rat Kv9.3 gene in CHO host cells       datasheet

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Gene

Species NCBI gene ID Chromosome Position
Human 3790 2 55111
Mouse 238076 12 61409
Rat 83588 6 56704
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Transcript

Species NCBI accession Length (nt)
Human NM_002252.5 2341
Mouse NM_173417.3 2933
Rat NM_031778.3 2311
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Protein Isoforms

Similarity to Kv9.1

The identity between Kv9.1 and Kv9.3 is only 54% within this conserved region, a rather low value in comparison with percentages higher than 70% found comparing members within the Kv1, Kv2 or Kv3 sub- families. If one would use 70% as a criterium to define subfamily membership, Kv9.3 could actually be a member of a new family, Kv10.1. The future cloning of additional homologue a-subunits will decide if Kv9.1 and Kv9.3 belong to the same or to two subfamilies [401]

Species Uniprot ID Length (aa)
Human Q9BQ31 491
Mouse Q8BQZ8 491
Rat O88759 491

Isoforms

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

PTM
Position
Type
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Structure

Kv9.3
Visual Representation of Kv9.3 Structure
Methodology for visual representation of structure available here

Kv9.3 predicted AlphaFold size

Species Area (Å2) Reference
Human 6108.64 source
Mouse 3980.74 source
Rat 5263.35 source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Kv9.3 heteromer with Kv2.1 in X.oocytes

Kv1.1 structure Kv1.1 structure To determine steadystate activation, conditioning pulses from -80 to +80 mV (increment: 10 mV) were applied, lasting 200 ms for Kv2.1 and 300 ms for Kv2.1/Kv9.3 to account for differences in activation kinetics. Subsequently, voltage was clamped to +40 mV, and the initial current in this segment was estimated from a monoexponential fit to its decay [177]. Kv2.1/Kv9.3 heteromers inactivate in a fast and complete fashion from intermediate closed states, but in a slow and incomplete manner from open states. Intermediate closed states of channel gating can be approached through partial activation or deactivation, according to a proposed qualitative model. These transitions are rate-limiting for Kv2.1/Kv9.3 inactivation. Finally, based on the kinetic description, we propose a putative function for Kv2.1/Kv9.3 heteromers in rat heart [1777]

Kv9.3 Co-transfected with Kv2.1 in CHO cells

Kv1.1 structure First, hKv2.1 transfected alone clearly deactivates faster at almost all voltages than do the others shown. Second, the cotransfected hKv2.1 and hKv9.1 produce a pretty good match to the 10–90% decay times determined from real HLEP. Cotransfected hKv2.1 and hKv9.3 tend to be even slower, but the results are not statistically significant. It is interesting to note that the variances of the channel parameters obtained from cotransfection experiments are significantly greater than those from natural lens currents or from transfection with Kv2.1 alone [1795]

Interaction of Kv9.3 and Kv2.1 in the Heart

A degenerate PCR-based strategy identified Kv1.2, Kv1.3, Kv2.1, and a novel K+ channel, Kv9.3, as potential oxygen-sensitive PA K+ channels. FIGURE 1F shows the expression of the various channels in lung, brain, conduit, and resistance pulmonary arter- ies by RT-PCR. Kv9.3 transfected cells did not express any exogenous channel activity. When Kv9.3 was coexpressed with Kv2.1, the activation threshold was shifted toward negative values (–50 mV), and the amplitude of the currents was greatly enhanced. Examination of the single-channel properties of Kv2.1 and Kv2.1/Kv9.3 revealed that Kv9.3 alters the single channel conductance of Kv2.1. The activity of both Kv2.1 and Kv2.1/Kv9.3 in excised inside-out patches was sensitive to the presence of internal ATP. When ATP concentration was lowered from 5 mM to 1 mM, channel activity was reduced by 55% [1851]

Interaction of Kv9.3 with Kv2.1 (rat) in X.oocytes

Kv9.3 increased the single-channel conductance of Kv2.1, from 8.5 to 14.5 pS. At the pharmacological level, the sensitivity to both 4-AP and TEA were reduced when Kv2.1 was co-expressed with Kv9.3. The alterations in the biophysical and pharmacological properties of Kv2.1 by Kv9.3 suggest that these two subunits associate to form a heteromultimer whose properties are different from that of the Kv2.1 [1871]

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Expression and Distribution

Kv9.3 Expression in Lungs

Kv9.1 is exclusively expressed in the brain, whereas Kv9.3 is more widely expressed, with the highest expression level in the lung [401]

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Function

Kv9.3 Function in Brain

Stromatoxin-sensitive, heteromultimeric Kv2.1/Kv9.3 channels contribute to myogenic control of cerebral arterial diameter [1849]

Kv9.3 Function in Rat Brain

The Kv2.1/Kv9.3 heteromer generates an O2 sensitive potassium channel and induces a slow deactivation that has important consequences for brain and lung physiology. We examined the developmental regulation of Kv2.1 and Kv9.3 mRNAs in brain and lung. Both genes followed parallel expression patterns in brain, increasing progressively through post-natal life. In lung, however, the expression of the two genes followed opposite trends: Kv2.1 transcripts decreased, while Kv9.3 mRNA increased. The Kv9.3/Kv2.1 ratio shows that while in brain the expression of both genes followed a similar pattern, the relative abundance of Kv9.3 increased steadily through post-natal life in lung. Furthermore, there is selective regulation of gene expression during the suckling-weaning transition. Our results suggest that different Kv9.3/Kv2.1 ratios could have physiological implications in both organs during post-natal development, and that diet composition and selective tissue-specific insulin regulation modulate the expression of Kv2.1 and Kv9.3 [1850]

Potassium channels form the most diverse class in the ion channel superfamily, giving rise to a large variety of currents, the kinetics of which are shaped to the requirements of their physiological function (Hille, B. 1992. Ionic Channels of Excitable Membranes. Sinauer Associates, Sunderland, MA). Part of this diversity is of combinatorial origin, inasmuch as potassium channels are oligomeric protein complexes [580], [744]. Participation of different proteins occurs by two mechanisms. Either distinct alpha-subunits assemble into heterotetrameric channels with all subunits lining the pore [741], [649], [745] or auxiliary beta-subunits associate with tetrameric channel complexes, changing their kinetic properties [312]. Modulatory alpha-subunits form a group of proteins that contributes to the diversity of potassium channels by the first mechanism. [177]

Kv9.2 is an alpha-subunit, highly similar to other Kv alpha-subunits by primary sequence, yet unable to form homomeric conducting channels in heterologous expression systems [746], [726], [400], [401].

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Interaction

Specific N-terminal interactions between Kv2- and modulatory alpha-subunits promote the assembly of heterotetrameric channels [399], [398], [747] displaying altered characteristics in comparison to homomeric Kv2 channels [726], [4, [748], [398].

References

177

Kerschensteiner D et al. Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation.
Biophys. J., 1999 Jul , 77 (248-57).

312

Rettig J et al. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
Nature, 1994 May 26 , 369 (289-94).

400

Salinas M et al. New modulatory alpha subunits for mammalian Shab K+ channels.
J. Biol. Chem., 1997 Sep 26 , 272 (24371-9).

401

Stocker M et al. Cloning and tissue distribution of two new potassium channel alpha-subunits from rat brain.
Biochem. Biophys. Res. Commun., 1998 Jul 30 , 248 (927-34).

649

Isacoff EY et al. Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes.
Nature, 1990 Jun 7 , 345 (530-4).

741

Christie MJ et al. Heteropolymeric potassium channels expressed in Xenopus oocytes from cloned subunits.
Neuron, 1990 Mar , 4 (405-11).

745

Ruppersberg JP et al. Heteromultimeric channels formed by rat brain potassium-channel proteins.
Nature, 1990 Jun 7 , 345 (535-7).

1795

Shepard AR et al. Electrically silent potassium channel subunits from human lens epithelium.
Am. J. Physiol., 1999 Sep , 277 (C412-24).

1850

Coma M et al. Different Kv2.1/Kv9.3 heteromer expression during brain and lung post-natal development in the rat.
J. Physiol. Biochem., 2002 Dec , 58 (195-203).

1851

Patel AJ et al. Kv2.1/Kv9.3, an ATP-dependent delayed-rectifier K+ channel in pulmonary artery myocytes.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (438-41).

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Credits

Contributors: Rajnish Ranjan, Michael Schartner, Katherine Johnston

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/32/ , accessed on 2024 Dec 21


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