Channelpedia

Kir2.3

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


Experimental data

Rat Kir2.3 gene in CHO host cells
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Gene

Species NCBI gene ID Chromosome Position
Human 3761 22 28872
Mouse 16520 15 32285
Rat 116649 7 27054

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Transcript

Species NCBI accession Length (nt)
Human NM_152868.3 2065
Mouse NM_008427.5 2152
Rat NM_053870.3 2656

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Protein Isoforms

Species Uniprot ID Length (aa)
Human P48050 445
Mouse P52189 445
Rat P52190 446

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

Kir2.3 predicted AlphaFold size

Species Area (Å2) Reference
Human 6802.03 source
Mouse 4669.75 source
Rat 5736.40 source

Methodology for AlphaFold size prediction and disclaimer are available here


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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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Expression and Distribution

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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CNS Sub-cellular 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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Function

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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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].


References

183

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

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).

190

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

191

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).

932

933

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

934

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).

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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To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/44/ , accessed on 2024 Dec 02



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