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



KV9.3 (also known as MGC9481) is member 3 of subfamily S of delayed-rectifier potassium voltage-gated channels and encoded by the gene KCNS3.

Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene 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. This gene belongs to the S subfamily of the potassium channel family.

Experimental data



RGD ID Chromosome Position Species
621527 6 34534529-34593882 Rat
731287 12 11097008-11157648 Mouse
731286 2 18059945-18114225 Human

Kcns3 : potassium voltage-gated channel, delayed-rectifier, subfamily S, member 3



Acc No Sequence Length Source
NM_031778 n/A n/A NCBI
NM_173417 n/A n/A NCBI
NM_001168564 n/A n/A NCBI
NM_002252 n/A n/A NCBI



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:0005737 cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. IEA
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA
GO:0005794 Golgi apparatus A compound membranous cytoplasmic organelle of eukaryotic cells, consisting of flattened, ribosome-free vesicles arranged in a more or less regular stack. The Golgi apparatus differs from the endoplasmic reticulum in often having slightly thicker membranes, appearing in sections as a characteristic shallow semicircle so that the convex side (cis or entry face) abuts the endoplasmic reticulum, secretory vesicles emerging from the concave side (trans or exit face). In vertebrate cells there is usually one such organelle, while in invertebrates and plants, where they are known usually as dictyosomes, there may be several scattered in the cytoplasm. The Golgi apparatus processes proteins produced on the ribosomes of the rough endoplasmic reticulum; such processing includes modification of the core oligosaccharides of glycoproteins, and the sorting and packaging of proteins for transport to a variety of cellular locations. Three different regions of the Golgi are now recognized both in terms of structure and function: cis, in the vicinity of the cis face, trans, in the vicinity of the trans face, and medial, lying between the cis and trans regions. IEA
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. 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
GO:0043231 intracellular membrane-bounded organelle Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. IEA



Similarity to Kv9.1

Aston- ishingly, 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 mem- ber of a new family, Kv10.1. The future cloning of addi- tional homologue a-subunits will decide if Kv9.1 and Kv9.3 belong to the same or to two subfamilies [401]



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].



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]

Edit - History


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].

Edit - History


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]



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).


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


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


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).

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

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).



Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia , accessed on [date]

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