Disease relevance of Kcnj10

• Treatment with soybean-derived Bowman Birk inhibitor increases serum prostate-specific antigen concentration while suppressing growth of human prostate cancer xenografts in nude mice [1].
• Kir4.1 expression confers the same K+ conductance to glioma membranes and a similar responsiveness to changes in [K+]o that characterizes differentiated astrocytes [2].

High impact information on Kcnj10

• We found that <10% of AQP4 immunogold labeling is retained in the perivascular astrocyte end-feet membranes of the alpha-Syn-/- mice, whereas labeling of the inwardly rectifying K+ channel, Kir4.1, is largely unchanged [3].
• Overall, these results indicate that Kir4.1 is the principal K(+) channel subunit expressed in mouse Müller glial cells [4].
• Of 11 members of the Kir channel family examined with reverse transcription-PCR, we could detect only expression of KAB-2 (Kir4.1) mRNA in stria vascularis [5].
• In vitro immunoprecipitation and pull-down assays demonstrated that Kir4.1 can bind directly to alpha-syntrophin, requiring the presence of the last three amino acids of the channel (SNV), a consensus PDZ domain-binding motif [6].
• Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes [7].

Biological context of Kcnj10

• The unique role of inward-rectifying potassium ion channels in membrane physiology coupled with previous strong association between ion channel gene mutations and seizure phenotypes puts even greater focus on Kcnj10 in the present model [8].
• Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene [8].
• A survey of the Kcnj10 SNP among other inbred mouse strains revealed a significant effect on seizure sensitivity such that most strains possessing a haplotype containing the B6 variant of Kcnj10 have higher seizure thresholds than those strains possessing the D2 variant [8].
• Quantitative trait loci mapping in mice led to identification of genetic variation in the potassium ion channel gene Kcnj10, implicating it as a putative seizure susceptibility gene [9].
• Judged by quantitative immunogold cytochemistry, deletion of the alpha-syntrophin gene causes a partial loss (by 70%) of aquaporin-4 labeling at astrocyte and Müller cell endfeet but no decrease in Kir4.1 labeling at these sites [10].

Anatomical context of Kcnj10

• 1. The most prominent labeling of the Kir4.1 protein was found in the endfoot membranes of Müller glial cells facing the vitreous body and surrounding retinal blood vessels [11].
• EP is generated by the high throughput of K(+) across cells of the stria vascularis, conferred partly by the activity of Kir4.1 channels [12].
• Heteromeric Kir4.1/5.1 was identified in the neocortex and in the glomeruli of the olfactory bulb [7].
• Kir4.1/5.1 and Kir4.1 expression appeared to occur only in astrocytes, specifically in the membrane domains facing the pia mater and blood vessels or in the processes surrounding synapses [7].
• Homomeric Kir4.1 was confined to the hippocampus and the thalamus [7].

Associations of Kcnj10 with chemical compounds

• Partial differentiation of the astrocytes with dibutyryl cAMP or by coculture with neurons has no effect on the Kir4.1 mRNA level [13].

Other interactions of Kcnj10

• Of these, the most compelling seizure susceptibility candidate is Kcnj10 [8].
• Transcripts encoding Kir2.1, Kir2.2, or Kir2.3, were encountered in a majority of cells, while Kir4.1 was less frequent [14].
• Differential effect of alpha-syntrophin knockout on aquaporin-4 and Kir4.1 expression in retinal macroglial cells in mice [10].
• 1. Immunolabeling using specific antibodies showed that channels comprising Kir4.1 and Kir5.1 subunits were assembled in a region-specific fashion [7].
• The amplitude of slow PIII, revealed by the nob genetic background, was reduced in Kir4.1+/- mice [15].

Analytical, diagnostic and therapeutic context of Kcnj10

• Stainings were found for the weakly inward-rectifying K(+) channel subunit Kir4.1 and for the strongly inward-rectifying K(+) channel subunit Kir2 [11].
• Immunoprecipitation experiments revealed that Kir4.1 is associated with the DGC in mouse brain and cultured cortical astrocytes [6].
• The functional consequences of CIPP expression on Kir4.1 channels were studied using whole-cell voltage clamp techniques in Kir4.1 transfected COS-7 cells [16].
• In situ hybridization experiments show that Kir4.1 mRNA is broadly distributed in the adult brain, including the neocortex, the stratum pyrimadale of the hippocampus, and the piriform cortex [13].
• Stellate cells in the neocortex and white matter are immunoreactive for Kir4.1, and double immunofluorescence experiments show colocalization of Kir4.1 and glial acidic fibrillary protein (GFAP) on stellate cells in the white matter [13].

References