Description: potassium inwardly-rectifying channel, subfamily J, member 2
Gene: Kcnj2     Synonyms: Kir2.1, IRK1, LQT7, SQT3, HHIRK1, HHBIRK1, KCNJ2

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KCNJ2 (also known as IRK1; LQT7; SQT3; ATFB9; HHIRK1; KIR2.1; HHBIRK1) encodes member 2 of subfamily J of potassium inwardly-rectifying channels, which is called Kir2.1. This channel has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Mutations in this gene have been associated with Andersen syndrome, which is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features.

Kir2.1, along with Kir2.2 and Kir2.3, is thought to underlie the background inward rectifier K+ current I K,ACh (Liu et al. 2001; [909] Zaritsky et al. 2001 [910]; Zobel et al. 2003 [911]). Kir2.1 channel underlies the cardiac current I K,1. Makary [182]



RGD ID Chromosome Position Species
61968 10 100574985-100576268 Rat
62261 11 110927478-110938139 Mouse
1352992 17 68165676-68176185 Human

Kcnj2 : potassium inwardly-rectifying channel, subfamily J, member 2



Acc No Sequence Length Source
NM_017296 n/A n/A NCBI
NM_008425 n/A n/A NCBI
NM_000891 n/A n/A NCBI



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: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: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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Caveolin-1 (cholesterol) suppresses Kir2.1

We whether Cav-1 regulates the function of Kir2.1 channels that play major roles in the regulation of membrane potential of numerous mammalian cells. Our earlier studies demonstrated that Kir2.1 channels are cholesterol sensitive. In this study, we show that Kir2.1 channels co-immunoprecipitate with Cav-1 and that co-expression of Kir2.1 channels with Cav-1 in HEK293 cells results in suppression of Kir2 current indicating that Cav-1 is a negative regulator of Kir2 function [1862]

Extracellular Spermine block

Kir3.1/Kir3.4 is more sensitive to extracellular spermine block than Kir2.1, and that intracellular and extracellular polyamines can permeate Kir3.1/Kir3.4, but not Kir2.1, to a limited extent. Makary [182]


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. Panama [183]

P639Amiodarone and Dronedarone

P639Amiodarone and dronedarone inhibit inwardly rectifying Kir2.1 channels, but not Kir2.2 and Kir2.3 channels [1863]


Chloroethylclonidine (CEC). The degree of current inhibition by CEC was found to vary with the membrane potential (approximately 70% block at -50 mV c.f. approximately 10% block at -190 mV). The kinetics of this voltage dependence were further investigated using recombinant inward rectifier K+ channels (Kir2.1) expressed in the MEL cell line [1865]

Mutation increases binding affinity

We find that a single mutation of tertiapin-Q increases the binding affinity for Kir2.1 by 5 orders of magnitude (K(d) = 0.7 nM). This potent blocker of Kir2.1 may serve as a structural template from which potent compounds for the treatment of various diseases mediated by this channel subfamily, such as cardiac arrhythmia, can be developed.


We examined if the subunits belonging to different subfamilies Kir2 and Kir3 can co-assemble to form heteromultimers in heterologous expression systems. We observed co-immunoprecipitation of Kir2.1 and Kir3.1 as well as Kir2.1 and Kir3.4 in HEK293T cells. Furthermore, analyses of subcellular localization using confocal microscopy revealed that co-expression of Kir2.1 promoted the cell surface localization of Kir3.1 and Kir3.4 in HEK293T cells. In electrophysiological experiments, co-expression of Kir2.1 with Kir3.1 and/or Kir3.4 in Xenopus oocytes and HEK293T cells did not yield currents with distinguishable features. However, co-expression of a dominant-negative Kir2.1 with the wild-type Kir3.1/3.4 decreased the Kir3.1/3.4 current amplitude in Xenopus oocytes. The results indicate that Kir2.1 is capable of forming heteromultimeric channels with Kir3.1 and with Kir3.4 [966]



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Cytoplasmic pore region of Kir2.1

Kv.11.1 Analysis of the crystal structure of the cytoplasmic domain of Kir2.1 has recently identified an intrinsically flexible loop around the membrane face of the cytoplasmic pore. The loop constricts the cytoplasmic pore to ∼3 Å and forms a girdle around the central pore axis. The girdle, which consists of a loop between βH and βI strands and is called the “G-loop,” forms the narrowest portion of the ion conduction pathway in the cytoplasmic region. The narrowest part of the G-loop is made up by A306 and to a lesser extent by E299, G300, M301, and M307. A306 is localized at the apex of the G-loop. The substitution of Glu, Cys, or Thr for A306 abolished Kir2.1 current. Because the side chain of these residues is larger than that of Ala, these substitutions would result in the physical occlusion of the G-loop without changing its backbone conformation. When another constituent of the G-loop M301 was mutated to Ala, an enhancement of inward rectification was observed [1861]

In Kir2.1, a number of residues within the pore lining second transmembrane domain and proximal C terminus have been shown to be important for inward rectification (Lu & MacKinnon, 1994 [912]; Stanfield et al. 1994 [913]; Yang et al. 1995 [919]; Kubo & Murata, 2001 [914]; Fujiwara & Kubo, 2002 [915]). Recent evidence suggests that these may not be the site of block, but instead shuttle the polyamines to their eventual binding site deeper within the pore (Kubo & Murata, 2001 [914]; Guo et al. 2003 [916]; Xie et al. 2003 [917]; Chang et al. 2003 [918]).



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Kir2.1 is an inwardly rectifying K+ channel, being expressed in the heart. Makary [182] More Kir2.1 in atrial myocytes compared with ventricular cells. Panama [183]

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AP Repolarization

I K1 - a current for which Kir2.1 mediates - regulates the late phase of action potential (AP) repolarization and stabilizes the resting membrane potential. In most species, the inward current density of atrial I K1 is significantly smaller than that of ventricles (Dhamoon [920], Giles [921], Melnik [922]).

QT Syndrome/Autism/Epilepsy

Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype [1864]


altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels. Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum–associated degradation (ERAD).

Cardiac Channel

There is an increasing body of evidence that heteromeric assembly of Kir2.1, Kir2.2 and Kir2.3 potassium channels is the molecular basis of cardiac IK1 current [1869]

Golgi Export

Here, we show that the potassium channel Kir2.1, mutations in which are associated with Andersen-Tawil syndrome, is selected as cargo into Golgi export carriers in an unusual signal-dependent manner. Unlike conventional trafficking signals, which are typically comprised of short linear peptide sequences, Golgi exit of Kir2.1 is dictated by residues that are embedded within the confluence of two separate domains. This signal patch forms a recognition site for interaction with the AP1 adaptor complex, thereby marking Kir2.1 for incorporation into clathrin-coated vesicles at the trans-Golgi

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Single Channel Conductance of Kir2.1

Kv.11.1 Representative current traces from -40 mV and -80 mV from HEK293T cells co-transfected with Kir2.1+GFP. In the control condition (absence of caveolin) the conductance of Kir was 21 pS [1862] Typical single channel behaviour of WT Kir2.1 channels in recordings from an inside-out patch at various holding potentials with the unitary conductance (g) averaging 29.1 ± 1.6 pS has been recorded [1856]

Rat Kir2.1 Skeletal Muscle Current Expressed in CHO

Kv.11.1 There was little outward current in response to small depolarizing pulses, but hyperpolarization resulted in large inward currents. Steps to voltages more positive than about 0 mV resulted in the additional activation of delayed rectifier currents. Qualitatively, control inward rectifier currents tended to saturate negative to about −150 mV [1865]

Mouse Kir2.1 Kinetics in CHO cells

Kv.11.1 The channels were heterologously expressed in CHO cells, a null cell line that almost completely lacks inward K1 current. A two-pulse voltage pro- tocol was used: 500-ms voltage steps from ÿ180 to 160 mV with increments of 10 mV and immediately followed by 10-ms test pulses to ÿ160 mV [1866]

Compared to Kir3

Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1. Makary [182]

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Markov Model of Kir2.1 interaction with PIP2

Kv.11.1 The values of the rate constants (α, β, δ, γ) were obtained by fitting to the mean open and closed times for the fully open state. To account for sublevels, we linked the fully open state (O1) to series of partially open states (Graphic), leading to a closed state (Cn) representing the unavailable mode. We assumed that the rate constants (α, β, δ) were identical for the sub level transitions [1856]

Model Kir21 (ID=44)       Edit

AnimalChinese Hamster
CellType CHO
Age 0 Days
Reversal -70.6 mV
Ion K +
Ligand ion
Reference [182] Samy M Y Makary et. al; J. Physiol. (Lond.) 2005 Nov 1
mpower 1.0
m Inf 1 /(1+exp((v-(-96.48))/23.26))
m Tau 3.7 +( -3.37 / (1 + exp((v - -32.9)/27.93)))
hpower 2.0
h Inf 1 /(1+exp((v-(-168.28))/-44.13))
h Tau 0.85 + (306.3 / (1 + exp((v - -118.29)/-27.23)))

MOD - xml - channelML



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


Lu Z et al. Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
Nature, 1994 Sep 15 , 371 (243-6).


Guo D et al. Interaction mechanisms between polyamines and IRK1 inward rectifier K+ channels.
J. Gen. Physiol., 2003 Nov , 122 (485-500).


Giles WR et al. Comparison of potassium currents in rabbit atrial and ventricular cells.
J. Physiol. (Lond.), 1988 Nov , 405 (123-45).


Melnyk P et al. Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle.
Am. J. Physiol. Heart Circ. Physiol., 2002 Sep , 283 (H1123-33).

Han H et al. Silencing of Kir2 channels by caveolin-1: cross-talk with cholesterol.
J. Physiol. (Lond.), 2014 Jul 18 , ().

Barrett-Jolley R et al. Direct block of native and cloned (Kir2.1) inward rectifier K+ channels by chloroethylclonidine.
Br. J. Pharmacol., 1999 Oct , 128 (760-6).

Romanenko VG et al. Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels.
Biophys. J., 2004 Dec , 87 (3850-61).

Kolb AR et al. ESCRT regulates surface expression of the Kir2.1 potassium channel.
Mol. Biol. Cell, 2014 Jan , 25 (276-89).

Kulzer M et al. Inhibition of cardiac Kir2.1-2.3 channels by beta3 adrenoreceptor antagonist SR 59230A.
Biochem. Biophys. Res. Commun., 2012 Jul 27 , 424 (315-20).


Ishihara K et al. Heteromeric assembly of inward rectifier channel subunit Kir2.1 with Kir3.1 and with Kir3.4.
Biochem. Biophys. Res. Commun., 2009 Mar 20 , 380 (832-7).

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Contributors: Rajnish Ranjan, Nitin Khanna

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