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
	Click for details 25 °C show 25 cells	Click for details 35 °C show 22 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

Known

NM_008427.5

2152

NP_032453.3

445

Predicted

XM_006520486.4

7039

XP_006520549.1

445

transcript variant X1

isoform X1

XM_006520488.4

5863

XP_006520551.1

445

transcript variant X3

isoform X1

XM_006520487.5

5854

XP_006520550.1

445

transcript variant X2

isoform X1

Known

NM_053870.3

2656

NP_446322.2

446

Predicted

XM_017594575.2

1950

XP_017450064.1

446

transcript variant X3

isoform X1

XM_006241964.4

2416

XP_006242026.1

446

transcript variant X2

isoform X1

XM_006241963.4

1864

XP_006242025.1

446

transcript variant X1

isoform X1

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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

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

[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].