Description: potassium inwardly-rectifying channel, subfamily J, member 14
Gene: Kcnj14     Synonyms: Kir2.4, IRK4, Kcnj14

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The channel kir2.4 encoded by the gene KCNJ14 (also known asIRK4; KIR2.4; KIAA1942; MGC46111) is an integral membrane protein and inward-rectifier type potassium channel, subfamily J, member 14, and probably has a role in controlling the excitability of motor neurons. Two transcript variants encoding the same protein have been found for this gene.

Strong inwardly rectifying K+ (KIR) channels have been described in many vascular and visceral tissues from different species (Quayle et al., 1997 [941];Nilius & Droogmans, 2001 [942]). These channels pass most current at potentials hyperpolarised to the K+ equilibrium potential (EK), though the small amount of outward carried at voltages depolarised to this potential, is enough to regulate the resting membrane potential (Em) and to cause blood vessel dilatation in response to either raised extracellular (10-15 mM) K+ (Quayle et al., 1997 [941]) or shear stress (Hoger et al., 2002 [943]). Since their initial identification in rat cerebral and coronary artery (Edwards et al., 1988 [944];Quayle et al., 1993 [945];Knot et al., 1996 [946]), patch-clamp studies have reported strongly rectifying inward currents in isolated lung endothelial and bronchial smooth muscle cells (Voets et al., 1996 [947];Kamouchi et al., 1997 [948];Snetkov & Ward, 1999 [949];Michelakis et al., 2001 [950];Hogg et al., 2002 [951];Oonuma et al., 2002 [952];Shimoda et al., 2002 [953]). Regardless of their origin within the cardiovascular system, KIR currents recorded to date are potently blocked by micromolar external Ba2+ ions in a manner that is steeply voltage and time-dependent (Quayle et al., 1993 [945];Robertson et al., 1996 [954];Bradley et al., 1999 [955];Snetkov & Ward, 1999 [949];Sakai et al., 2002 [956];Oonuma et al., 2002 [952]). Summary from [940].



Kir2.4 (IRK4), which shares 53-63% similarity to Kir2.1, Kir2.2, or Kir2.3 on the amino acid level. Toepert [959]

RGD ID Chromosome Position Species
628872 1 96293795-96297747 Rat
735433 7 53071837-53080117 Mouse
735432 19 48958766-48969367 Human

Kcnj14 : potassium inwardly-rectifying channel, subfamily J, member 14



Acc No Sequence Length Source
NM_170718 n/A n/A NCBI
NM_145963 n/A n/A NCBI
NM_013348 n/A n/A NCBI
NM_170720 n/A n/A NCBI



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Kir2.4 co expressed with Kir2.1

Kv.11.1 Co-expression of either dominant negative Kir2.1 or Kir2.4 subunits in Xenopus oocytes with either wild-type Kir2.1 or 2.4 strongly decreased resulting current amplitude. To examine physical association between Kir2.1 and Kir2.4, Cos-7 cells were co-transfected with a His6-tagged Kir2.1 subunit (Kir2.1-His6) and a FLAG-tagged Kir2.4 subunit (Kir2.4-FLAG). After pulldown with a His6-binding resin, Kir2.4-FLAG could be detected in the eluted cell lysate by Western blotting, indicating co-assembly of Kir2.1-His6 and Kir2.4-FLAG. These results show that Kir2.4 subunits can co-assemble with Kir2.1 subunits, and that co-assembled channels are functional, with properties different from those of Kir2.4 or Kir2.1 alone. Since Kir2.1 and Kir2.4 mRNAs have been shown to co-localize in the CNS, Kir2.1 and Kir2.4 heteromultimers might play a role in the heterogeneity of native inward rectifier currents [925]


Cloned Kir2.4 and KIR currents in HPASM cells showed little voltage dependence to Ba2+ inhibition, which blocked at a more superficial site than for Kir2.1. [940]


Expression of human Kir2. 4 cRNA in Xenopus oocytes generated strong, inwardly rectifying K(+) currents that were enhanced by extracellular alkalinization. Human Kir2.4 encodes an inwardly rectifying K(+) channel that is preferentially expressed in the neural retina and that is sensitive to physiological changes in extracellular pH. [958]

Ba2+ andCs+

Similar to other Kir2 channels, Kir2.4 is susceptible to block by the extracellular cations Ba2+ and Cs+, but with considerable differences in affinity. The voltage dependence of the Cs+ occlusion between −80 mV and −150 mV membrane potential may indicate Cs+ binding at deeper sites in the open pore where it crossed part of the membrane electric field. Quantitative analysis demonstrated that a tenfold change in K i (i.e., the concentration of Cs+ producing 50% block) corresponded to a change in membrane potential of 36 mV similar to other Kir2 channels [959]





These channels form as tetramers of subunits that have only two membrane- spanning regions between which is the H5 loop responsible for potassium selectivity. Four isoforms have been identified, Kir2.1, 2.2, 2.3 and 2.4 (Stanfield et al., 2002 [957]).



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At the molecular level, the Kir2.0 subfamily almost certainly encode the classical inward rectifiers found in the brain, heart, skeletal and vascular muscle (Quayle et al., 1997 [941];Stanfield et al., 2002 [957]). From [940].

Kir2.4 was found in the neural retina. [958]

Expression of Kir2.4 in Rat Brain

In situ hybridization analysis identifies Kir2.4 as the most restricted of all Kir subunits in the brain. Kir2. 4 transcripts are expressed predominantly in motoneurons of cranial nerve motor nuclei within the general somatic and special visceral motor cell column and thus are uniquely related to a functional system. Toepert [959]

X-ray film autoradiographs of sagittal (A) and coronal (B) sections show high mRNA expression in nuclei of the special visceral motor cell column, in the hypoglossal nucleus, and in the choroid plexus [959]

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Kir2.4 channels are of major importance in controlling excitability of motoneurons in situ. Toepert [959]

Strong inwardly rectifying K+ (KIR) channels that contribute to maintaining the resting membrane potential are encoded by the Kir2.0 family (Kir2.1-2.4). [940]

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Rat Kir2.4 expressed in X.oocytes

Kv.11.1 Kir2.4 cRNA was injected into Xenopus oocytes, and expression was assayed 2 d later to characterize the functional properties of Kir2.4 channels. Compared with the minute background inward current in uninjected or water-injected control oocytes (114 ± 28 nA; n = 5), Kir2.4-injected oocytes showed inward current amplitudes that averaged 1244 ± 482 nA in 2 mM [K+]e and 7583 ± 2031 nA (n = 7 each) in 96 mM “high” [K+]e (V h = −100 mV). Similarly prominent currents of 1128 ± 674 pA (n = 5) were obtained when Kir2.4 was expressed in COS-7 cells (25 mM[K+]e). As expected from the primary amino acid sequence, macroscopic Kir2.4 currents with respect to kinetics, activation potentials, rectification, and K+ permeability in both expression systems revealed properties typical of Kir2 subfamily members. In response to hyperpolarizing voltage steps between −60 and −140 mV, “gating” of Kir2.4 channels was rapid, with time constants of 0.88 ± 0.05 msec (n = 13) in 96 mM[K+]e [959]

Kir2.4 expressed in COS-7 Cells

Kv.11.1 Injection of either subunit alone produced robust inward rectifier currents (left panels).

Single Channel Conductance of Kir2.4

Single-channel recordings revealed strong inwardly rectifying channels with an average conductance of 21 pS in HPASM cells, not significantly different from either Kir2.1 (19.6 pS) or Kir2.4 (19.4 pS). Reverse-transcription polymerase chain reaction detected products corresponding to Kir2.1, Kir2.2 and Kir2.4 but not Kir2.3. We demonstrate that cultured HPASM cells express K(IR) channels and suggest both Kir2.1 and Kir2.4 subunits contribute to these channels, although the whole-cell current characteristics described share more similarity with Kir2.4 [940]





Quayle JM et al. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.
Physiol. Rev., 1997 Oct , 77 (1165-232).


Nilius B et al. Ion channels and their functional role in vascular endothelium.
Physiol. Rev., 2001 Oct , 81 (1415-59).


Hoger JH et al. Shear stress regulates the endothelial Kir2.1 ion channel.
Proc. Natl. Acad. Sci. U.S.A., 2002 May 28 , 99 (7780-5).


Edwards FR et al. Inward rectification in rat cerebral arterioles; involvement of potassium ions in autoregulation.
J. Physiol. (Lond.), 1988 Oct , 404 (455-66).


Voets T et al. Membrane currents and the resting membrane potential in cultured bovine pulmonary artery endothelial cells.
J. Physiol. (Lond.), 1996 Nov 15 , 497 ( Pt 1) (95-107).


Kamouchi M et al. Modulation of inwardly rectifying potassium channels in cultured bovine pulmonary artery endothelial cells.
J. Physiol. (Lond.), 1997 Nov 1 , 504 ( Pt 3) (545-56).


Michelakis ED et al. Potassium channels regulate tone in rat pulmonary veins.
Am. J. Physiol. Lung Cell Mol. Physiol., 2001 Jun , 280 (L1138-47).


Shimoda LA et al. Inhibition of inwardly rectifying K(+) channels by cGMP in pulmonary vascular endothelial cells.
Am. J. Physiol. Lung Cell Mol. Physiol., 2002 Aug , 283 (L297-304).


Bradley KK et al. Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells.
J. Physiol. (Lond.), 1999 Mar 15 , 515 ( Pt 3) (639-51).


Stanfield PR et al. Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
Rev. Physiol. Biochem. Pharmacol., 2002 , 145 (47-179).


Hughes BA et al. Cloning and functional expression of human retinal kir2.4, a pH-sensitive inwardly rectifying K(+) channel.
Am. J. Physiol., Cell Physiol., 2000 Sep , 279 (C771-84).



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