Description: potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1
Gene: Kcns1     Synonyms: Kv9.1, kcns1

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KV9.1 is member 1 of subfamily S of potassium voltage-gated delayed-rectifier channels, encoded by the gene KCNS1.

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 KCNS1 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

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In contrast to the genes in the other subfamilies, members of the Kv8 and Kv9 subfamilies have been found to be incapable of forming functional channels when expressed either in oocytes or cell lines. Moreover, these mammalian genes appear to have no Drosophila homologs. [402]

RGD ID Chromosome Position Species
621524 3 155103400-155110718 Rat
735721 2 163989355-163996849 Mouse
735720 20 43720950-43729753 Human

Kcns1 : potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1



Acc No Sequence Length Source
NM_053954 n/A n/A NCBI
NM_008435 n/A n/A NCBI
NM_002251 n/A n/A NCBI



Accession Name Definition Evidence
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. ISS
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. ISS
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: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: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: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

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Kv2.1 and Kv2.2 Co-assembly

Since previous studies have suggested that Kv9.1 function is linked to coassembly with Kv2.1 and Kv2.2 subunits, we investigated whether Kv9.1 and Kv2 subunits are coexpressed in DRG neurons. To achieve this, we performed ISH for Kv9.1/Kv2.1 (left) and Kv9.1/Kv2.2 (right) in adjacent DRG sections and were able to directly observe colocalization of these mRNAs in single medium-large neurons (arrows). Examining the Kv9.1-positive population, we found that 48.6 and 76.9% of cells coexpressed Kv2.1 or Kv2.2, respectively. The presence of both Kv2 subunits was documented in more than a third of all Kv9.1-positive neurons (36.7%), while only a small number did not express any Kv2 subunit (11.25%) [1775]

The Kv9.1 gene encodes a potassium channel alpha subunit that is expressed in a variety of neurons, including those of the inferior colliculus. When cRNA encoding this subunit is injected into Xenopus oocytes, no functional channels are expressed. Kv9.1 isolated from a rat brain cDNA library alters the kinetics and the voltage-dependence of activation and inactivation of Kv2.1, a channel subunit that generates slowly inactivating delayed rectifier potassium currents. The rate of activation of Kv2.1 is slowed by co-expression with Kv9.1. With Kv2.1 alone, the amplitude of evoked currents increases monotonically with increasing command potentials. In contrast, when Kv2.1 is co-expressed with Kv9.1, the amplitude of currents increases with increasing depolarization up to potentials of only ∼+60 mV, after which increasing depolarization results in a decrease in current amplitude. [402]



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Kv9.1 and Kv9.2 are neuronal modulatory alpha subunits that define a structural family designated as Kv9. They modulate Kv2.alpha subunits but have no functional activity by themselves. [400]



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Expression of Kv9.1 in DRG sections of Rats

We first examined the expression of Kv9.1 transcripts in lumbar DRG sections of naive rats, using ISH. Size-frequency analysis revealed that Kv9.1 mRNA was robustly expressed in medium-large (>30 μm diameter, 89.7 ± 1.5%), but not small (<30 μm diameter, 5.6 ± 1.4%) neurons [1755]

Kv9.1 and Kv9.2, two known members of the Kv9 subfamily, appear to be expressed diffusely in cells of the inferior colliculus [402].

Kv9.1 Expression in Rat Brain

High levels of expressions are found in the olfactory bulb, cerebral cortex, hippocampal formation, habenula, basolateral amygdaloid nuclei, and cerebellum. Interestingly Kv9.1 and Kv9.2 colocalized with Kv2.1 and/or Kv2.2 α subunits in several regions of the brain [400]

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Inhibitor of Neuronal Excitability

Our study is the first one to address the effect of Kv9.1 in vivo and our results strongly suggest that, in sensory neurons, Kv9.1 is an inhibitor of neuronal excitability [1775]. Interestingly, Kv9.1 is not a pore-forming subunit and therefore its influence on sensory neuron excitability must be indirect [400]

K+ channel functions are included in very diverse processes such as neuronal integration, cardiac pacemaking, muscle contraction, and hormone secretion in ex- citable cells [735], as well as in cell proliferation, cell volume regulation, and lymphocyte differentiation [736].

Kv9.1 and Kv9.2 modulate Kv2.alpha subunits but have no functional activity by themselves [400]. I.e., the kinetics of activation and the voltage-dependence of Kv2.1 currents are altered by such co-expression with Kv9.1 [402].

Hyper excitability

Of particular interest, we illustrate that Kv9.1 dysfunction can also trigger a form of stimulus-dependent hyperexcitability in sensory neurons. This firing did not depend on any CNS connection as it was observed in axons that were centrally disconnected [1775]

Neuropathic Pain

Our results propose that Kv9.1 downregulation after nerve injury may be the molecular switch controlling myelinated sensory neuron hyperexcitability. Intriguingly, a recent wide-genome association screen in humans identified a Kv9.1 polymorphism associated with susceptibility to develop chronic neuropathic pain after back surgery or leg amputation, suggesting that the mechanisms described in our studies will be of direct clinical relevance to human pain [1775] [1794]

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Kv9.1 Kinetics affect Kv2.2 and Kv1.3

Kv1.1 structure [402] It is likely that the association of Kv9.1 with functional channel subunits such as Kv2.1 alters their properties in ways other than the relatively minor changes in kinetics and voltage dependence described here. In particular, ‘silent’ subunits, such as Kv9.1, may add new sites for modulation by protein kinases and other second messengers, or may target the resultant channel complex to specific subcellular locations within a neuron. Determination of its real function in neurons, such as those of the inferior colliculus, may eventually require investigation of native potassium currents and firing patterns in cells in which the Kv9.1 gene has been deleted [402]

Kv9.1 interacts with Kv2.1 in CHO cells

In our experiments, both hKv9.1 and hKv9.3 slowed the deactivation and inactivation of hKv2.1-dependent currents, in keeping with previous results (18, 26). Interestingly, with the cotransfection of either electrically silent subunit with hKv2.1, inactivation and deactivation time courses more closely matched those measured from native human lens cells than did the time courses measured from hKv2.1 alone. Transfection with either hKv2.1-hKv9.1 or hKv2.1-hKv9.3 fusion proteins produces about the same slowing of activation as cotransfection of unfused subunits [1795]






Cahalan MD. et al. Potassium and calcium channels in lymphocytes.
Annu. Rev. Immunol., 1995 , 13 (623-53).


Pongs O. et al. Structure-function studies on the pore of potassium channels.
J. Membr. Biol., 1993 Oct , 136 (1-8).


Lu Z. et al. Mutations in the K+ channel signature sequence.
Biophys. J., 1994 Apr , 66 (1061-7).


MacKinnon R. et al. Pore loops: an emerging theme in ion channel structure.
Neuron, 1995 May , 14 (889-92).


Brown AM. et al. K+ pore structure revealed by reporter cysteines at inner and outer surfaces.
Neuron, 1995 May , 14 (1055-63).



Tempel BL. et al. Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons.
Nature, 1993 Sep 2 , 365 (75-9).


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


Kerschensteiner D. 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).


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

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