Channelpedia

Kir2.3

Description: potassium inwardly-rectifying channel, subfamily J, member 4
Gene: Kcnj4     Synonyms: Kir2.3, HIR, HRK1, IRK3, HIRK2

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Introduction

One class of potassium channels is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by KCNJ4 (also known as HIR; HRK1; IRK3; HIRK2; IRK-3; Kir2.3; MGC142066; MGC142068) encodes the potassium inwardly-rectifying channel, subfamily J, member 4, named Kir2.3, which is an integral membrane protein. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. http://www.ncbi.nlm.nih.gov/gene/3761

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Gene

RGD ID Chromosome Position Species
621436 7 117601723-117616019 Rat
733317 15 79314144-79335671 Mouse
733316 22 38822332-38851203 Human

Kcnj4 : potassium inwardly-rectifying channel, subfamily J, member 4

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Transcript

Acc No Sequence Length Source
NM_053870 n/A n/A NCBI
NM_008427 n/A n/A NCBI
NM_004981 n/A n/A NCBI
NM_152868 n/A n/A NCBI
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Ontology

Accession Name Definition Evidence
GO:0043025 neuronal cell body The portion of a neuron that includes the nucleus, but excludes all cell projections such as axons and dendrites. IDA
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: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:0030425 dendrite A neuron projection that has a short, tapering, often branched, morphology, receives and integrates signals from other neurons or from sensory stimuli, and conducts a nerve impulse towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. IDA
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Interaction

Free intracellular polyamines (PAs) are the key determinants of rectification in IK1 and Kir2 channels (Lopatin [931]). Yan et al. [930] provided evidence that different concentrations of free PAs may underlie differences between atrial and ventricular IK1 in the guinea pig heart.

Inclusion of only one Kir2.3 subunit to a Kir2.1 channel led to an approximate threefold slowing of activation kinetics, with greater slowing on subsequent additions of Kir2.3 subunits. Activation kinetics of IK1 in both ventricles and both atria was found to correspond to fast-activating Kir2.1/Kir2.2 channels, suggesting no major contribution of Kir2.3 subunits. Panama [183]

Kir2.3 is modulated by ATP (Collins et al., 1996 [933]), protein kinase C (PKC) (Henry et al., 1996 [934]), G protein beta-gamma subunits (Cohen et al., 1996 [935]), Mg2+ (Chuang et al., 1997 [936]), pH (Coulter et al., 1995 [937]; Zhu et al., 1999a [938]), arachidonic acid (AA) (Liu et al., 2001 [188]) and the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate (PIP2) (Du et al., 2004 [939]). Listed by Wang [188].

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Protein

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Structure

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Distribution

Subcellular Localization of Kir2.3

Immunoelectron microscopy of the OB revealed that Kir2.3 immunoreactivity was specifically clustered on the postsynaptic membrane of asymmetric synapses between granule cells and mitral/tufted cells [1879]

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Expression

Expression of Kir2.3 in Mouse Brain

Although Kir2.3 is known to be expressed abundantly in the forebrain, its precise localization has not been identified. Using an antibody specific to Kir2.3, we examined the subcellular localization of Kir2.3 in mouse brain. Kir2.3 immunoreactivity was detected in a granular pattern in restricted areas of the brain, including the olfactory bulb (OB) [1879]

Expression of Kir2.3 in Rat Brain

we have provided both immunohisto- chemical and electrophysiological evidence that the Kir2.3 strong inward rectifier channel is expressed in astrocytes of both polygonal and stellate morphology, from both adult and neonatal rat brain, both in vivo and in vitro. Given the importance of this channel in maintaining the resting potential of polygonal reactive astrocytes [1880]

Expression of Kir2.3 in Mammalian CNS

Kir2.3 has previously been identified in mammalian CNS forebrain (Lesage et al., 1994; Morishige et al., 1994; Bredt et al., 1995; Karschin et al., 1996; Stone- house et al., 1999), in nodes of Ranvier (Mi et al., 1996), and in renal epithelial cells (Welling, 1997) [1880]

Kir2.3 is highly expressed in the heart and brain (Perier 1994 [14).

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Functional

Kirs2.3 function in Rat Cardiomyocytes

A major finding of this study is that Kir2.3 channel subunit is essential for normal native IK1 currents in the neonatal rat cardiomyocytes. Previous studies showed that the deletion of Kir2.1 subunit almost eliminated the IK1 currents, and the deletion of Kir2.2 subunit reduced the IK1 currents by 50% [15]. Our data demonstrated that IK1 current densities in the Kir2.3 knock-down cardiomyocytes were decreased by about 80%. Therefore, Kir2.3 subunit also plays an important role in IK1 currents.

IN cardiac myocytes the inward rectifier potassium current, IK1, regulates the late phase of action potential (AP) repolarization and stabilizes the resting membrane potential. IK1 channels are believed to be homo- and/or heterotetramers of Kir2.1, Kir2.2, and Kir2.3 subunits from the Kir2 family of inward rectifier potassium channels (Lopatin [926], Nichols [928]). A number of studies consistently indicated that the species-dependent (Dhamoon [920]) and tissue-specific expression (Schram [929]) of different Kir2 subunits may contribute, at least in part, to its variability. There is evidence that, in mouse ventricles, Kir2.1 is the major isoform with a significant contribution of Kir2.2, although knockout of both genes revealed the presence of another slowly activating component characteristic of Kir2.3 subunits (Zaritzki [910]).

Temporal Lobe Epilepsy

Kir2.3, has been found down-regulated in the hippocampus of chronic temporal lobe epileptic (cTLE) patients which may underline the mechanism of epilepsy. Our results suggest that the down-regulation of the Kir2.3 channel expression might contribute to the pathogenesis of TLE, which may be ameliorated by the administration of tenidap [1881]

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Kinetics

Human Kir2.3 in CHO cells Kinetics

Kv.11.1 whole-cell Kir2.3 currents in response to a series of 250 ms voltage steps from −127 mV to +23 mV (10 mV increments) before (ctrl), during Arachidonic Acid (AA), and after (wash) application of 10 μM AA [190]

Single Channel Conductance of Kir2.3

Kv.11.1 [188]

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Model

References

189

Shyng SL et al. Depletion of intracellular polyamines relieves inward rectification of potassium channels.
Proc. Natl. Acad. Sci. U.S.A., 1996 Oct 15 , 93 (12014-9).

183

Panama BK et al. Heterogeneity of IK1 in the mouse heart.
Am. J. Physiol. Heart Circ. Physiol., 2007 Dec , 293 (H3558-67).

191

Dyachenko V et al. Mechanical deformation of ventricular myocytes modulates both TRPC6 and Kir2.3 channels.
Cell Calcium, 2009 Jan , 45 (38-54).

926

Lopatin AN et al. Inward rectifiers in the heart: an update on I(K1).
J. Mol. Cell. Cardiol., 2001 Apr , 33 (625-38).

928

Nichols CG et al. Inward rectifier potassium channels.
Annu. Rev. Physiol., 1997 , 59 (171-91).

933

Collins A et al. A strongly inwardly rectifying K+ channel that is sensitive to ATP.
J. Neurosci., 1996 Jan , 16 (1-9).

935

Cohen NA et al. Inhibition of an inward rectifier potassium channel (Kir2.3) by G-protein betagamma subunits.
J. Biol. Chem., 1996 Dec 13 , 271 (32301-5).

938

Zhu G et al. Effects of intra- and extracellular acidifications on single channel Kir2.3 currents.
J. Physiol. (Lond.), 1999 May 1 , 516 ( Pt 3) (699-710).

190

Liu Y et al. Direct activation of an inwardly rectifying potassium channel by arachidonic acid.
Mol. Pharmacol., 2001 May , 59 (1061-8).

1879

Inanobe A et al. Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses.
Am. J. Physiol., Cell Physiol., 2002 Jun , 282 (C1396-403).

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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/ionchannels/44/ , accessed on [date]