Disease relevance of KCNJ4

• Our results demonstrate that tenidap is a potent opener of hKir2.3 and suggest that it can serve as a valuable pharmacological tool for studying physiological and pathological processes involving Kir2.3 [1].
• Among homomeric Kirs, we have found that even the most sensitive Kir1.1 and Kir2.3 have pK approximately 6.8, suggesting that they may not be capable of detecting hypocapnia [2].

High impact information on KCNJ4

• (v) Kir2.1 and Kir2.3 channels could be coimmunoprecipitated in membrane extracts from isolated guinea pig cardiomyocytes [3].
• The aim of our study was to find out whether heteromerization of Kir2.1 channels with wild-type Kir2.2 and Kir2.3 channels contributes to the phenotype of Andersen's syndrome [3].
• CONCLUSIONS: mRNAs for all 4 IRKs are detected in human atrium and ventricle, but the mRNA copy number of a low-conductance subunit (HIR) is larger in atrium and the copy number of a weakly rectifying subunit (TWIK-1) is larger in ventricle [4].
• We have isolated a human hippocampus cDNA that encodes an inwardly rectifying potassium channel, termed HIR (hippocampal inward rectifier), with strong rectification characteristics [5].
• In this study, we showed that deletion of HIR genes, which regulate histone gene expression, synergistically reduced gene silencing at telomeres and at the HM loci in cacDelta mutants, although hirDelta mutants had no silencing defects when CAF-I was intact [6].

Biological context of KCNJ4

• Suppression of Kir2.3 activity by protein kinase C phosphorylation of the channel protein at threonine 53 [7].
• Kir2.3 plays an important part in the maintenance of membrane potential in neurons and myocardium [7].
• Additional electrophysiological experiments showed that Kir2.3 channel down-regulation was blocked by the phospholipase C inhibitors, neomycin (100 microm) and D609 (200 microm) [8].
• However, deletion of combinations of CAC and HIR genes also affected the growth rate and in some cases caused partial temperature sensitivity, suggesting that global aspects of chromosome function may be affected by the loss of members of both gene families [6].
• In HIR B expressing cells, no significant differences in association and dissociation kinetics were observed [9].

Anatomical context of KCNJ4

• RNA blot analyses show that HIR transcripts are present in heart, skeletal muscle, and several different brain regions, including the hippocampus [5].
• When HRK1 was expressed in Xenopus oocytes, large inward K+ currents were observed below the K+ reversal potential but very little outward K+ current was observed [10].
• The functional properties of HRK1 are very similar to those of glial cell inward rectifier K+ channels and HRK1 may represent a glial cell inward rectifier [10].
• In contrast, G-protein-gated inward rectifier potassium channel-4 immunoreactivity was restricted to some neuronal populations, such as Purkinje cells and neurons of the globus pallidus and the ventral pallidum [11].
• Kir4.1 in retinal glial cells and Kir2.1, Kir2.3 and Kv1.5 in Schwann cells have been identified [12].

Associations of KCNJ4 with chemical compounds

• HRK1 currents were blocked by external Ba2+ and Cs+ (K(0) = 183 microM, and K(-130) = 30 microM, respectively), and internal tetraethylammonium ion (K(0) = 62 microM), but were insensitive to external tetraethylammonium ion [10].
• The voltage dependence of spermine unblock was similar in all Kir2 channels, but the rates of unblock were approximately 7-fold and approximately 16-fold slower in Kir2.3 channels than those in Kir2.1 and Kir2.2 when measured at high and physiological extracellular K+, respectively [13].
• 3. Also, buffering the intracellular calcium concentration with a high concentration of EGTA abolished the m1 receptor-induced inhibition of Kir2.1-Kir2.3, implicating a role for calcium in these responses [14].
• Interestingly, preincubation with human-specific anti-insulin receptor antibody abolished the increased insulin sensitivity in glucose incorporation into glycogen in HIR delta 978 cells [15].
• Regions of the hippocampal inward rectifier potassium channel Kir 2.3 that contact the aqueous environment were investigated by identification of native cysteine residues that confer sulfhydryl reagent sensitivity to the channel conductance [16].
• In yeast three-hybrid studies, the Kir2.3 di-isoleucine motif does not bind the AP-2 alphaC-sigma2 hemicomplex in the way that has been recently observed for canonical di-leucine signals [17].

Physical interactions of KCNJ4

• Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+]o were similar to Kir2.1 but not Kir2 [18].

Other interactions of KCNJ4

• Western blot analysis showed clear Kir2.1 and Kir2.2 protein expression, but Kir2.3 protein was undetectable [19].
• Among others, genes for dopamine receptor D2 (DRD2) and the inwardly rectifying potassium channel (Kir2.3) were found to be over-expressed in microarray analysis [20].

Analytical, diagnostic and therapeutic context of KCNJ4

• RT-PCR of mRNA from proliferative cells identified transcripts for Kir2.1 and Kir2.2 but not Kir2.3 potassium channels [21].
• Immunofluorescence study showed that cells co-expressed TGF-beta(1) receptors 1 and 2, Kir2.3, and glial fibrillary acidic protein (GFAP) [8].
• Therefore, we studied the mechanisms mediating the regulation of Kir2.1-Kir2.3 by the G-protein-coupled m1 muscarinic receptor using the whole-cell patch-clamp technique and recombinant expression in the tsA201 mammalian cell line [14].
• 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 [22].

References