Kcnj11 _ Kir6.2 Antibody
- Known as:
- Kcnj11 _ Kir6.2 Antibody
- Catalog number:
- AF1586a
- Product Quantity:
- 0.1mg
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- Kcnj11 _ Kir6.2 Antibody
Related genes to: Kcnj11 _ Kir6.2 Antibody
- Gene:
- KCNJ11 NIH gene
- Name:
- potassium voltage-gated channel subfamily J member 11
- Previous symbol:
- -
- Synonyms:
- Kir6.2, BIR
- Chromosome:
- 11p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-09-12
- Date modifiied:
- 2018-03-06
Related products to: Kcnj11 _ Kir6.2 Antibody
Related articles to: Kcnj11 _ Kir6.2 Antibody
- Most antipsychotic drugs (APDs) cause hyperphagia and weight gain, yet the neural mechanisms underlying these metabolic side effects remain elusive, in part due to difficulties in modeling them in rodents. Here, we establish a mouse model that recapitulates clozapine-induced metabolic syndrome, enabling mechanistic investigation of this widely prescribed APD. We show that clozapine promotes obesity in female mice by driving hyperphagia, which requires functional coupling between the melanocortin 4 receptor (MC4R) and the Kir7.1 potassium channel. Within the broader context of clozapine's polypharmacology, this signaling axis emerges as a critical downstream convergence node for APD-induced metabolic dysfunction. Mechanistically, clozapine inhibits MC4R-expressing neurons in the paraventricular nucleus of the hypothalamus by enhancing MC4R-Kir7.1 coupling, thereby increasing inward potassium currents. Notably, clozapine produces this inhibition without binding the MC4R orthosteric site and without engaging canonical Gαs signaling. Genetic deletion of Kir7.1 in MC4R neurons or pharmacological inhibition of Kir7.1 reverses clozapine-induced weight gain while preserving its behavioral efficacy in established antipsychotic assays. Together, these findings reveal a G-protein-independent mechanism by which clozapine disrupts energy balance and identify MC4R-Kir7.1 coupling as a therapeutically tractable pathway for mitigating APD-associated metabolic dysfunction. - Source: PubMed
Publication date: 2026/09/03
Li LiHernandez Ciria CGimenez Luis EXu BaijieDahir Naima SPeisley AlysWu ZanChen MeilinSerrato AlexandraWan RongSwati Birnbaum Shari GCone Roger DLiu Chen - KirBac1.1 is a prokaryotic homolog of mammalian inward-rectifier potassium (Kir) channels, and the functional equilibrium of KirBac1.1 is highly dependent on the type of membrane lipids. Like Kir channels, KirBac1.1 activity is also inhibited by cholesterol, a physiologically relevant lipid in human health and disease. Despite the slide helix is an important functional motif during lipid-dependent gating, the structural dynamics of the slide helix during cholesterol-induced channel inactivation is not well understood and is the focus of this work. Sequence analysis reveals that the slide helix of KirBac1.1 itself is a putative cholesterol-recognition motif. Liposomal K+ flux assays show that transport activity of the wild-type channel in PC/PG membranes is completely abolished at high concentration of cholesterol, whereas this is not observed in some of the single-cysteine mutants of the slide helix, indicating slide helix residues are critical for cholesterol sensitivity. Quenching of intrinsic Trp fluorescence upon increasing cholesterol concentration strongly suggests that the KirBac1.1 functional inhibition by cholesterol is possibly due to its direct interaction with the channel. Membrane penetration depth measurements using NBD-labeled slide helix residues clearly show relatively shallow membrane interfacial localization of the slide helix in cholesterol-containing membranes that is associated with significant structural dynamics changes and altered conformational heterogeneity. Based on distance measurements in varying membrane lipid compositions that stabilize the active and inactive conformations, we hypothesize that slide helix position in the membrane might possibly act as a "conformational switch" in regulating the KirBac1.1 function. These results involving dynamic lipid-protein interactions in lipid-dependent gating might be relevant for other Kir channels. - Source: PubMed
Publication date: 2026/08/06
Bysack ArpanRaghuraman H - KATP-channel-related hyperinsulinism (KATPHI) is a rare genetic disorder of the pancreatic beta cells, manifesting as life-threatening hypoglycemia in neonates due to excessive insulin secretion. Management of the severe diffuse form of KATPHI currently lacks treatment options, as the first-line therapy octreotide is often insufficiently effective, necessitating radical pancreatectomy in many patients. - Source: PubMed
Lithovius VäinöMontaser HossamSaarimäki-Vire JonnaIbrahim HazemBarsby TomBalboa DiegoOtonkoski Timo - Glioblastoma (GBM) exhibits profound metabolic plasticity and resistance to conventional therapies, partly driven by mitochondrial adaptability and stress response mechanisms. ONC212, a second-generation imipridone, targets mitochondrial proteostasis, yet determinants of tumour sensitivity remain unclear. This study aimed to investigate whether ATP-sensitive potassium (KATP) channel expression modulates ONC212-induced mitochondrial dysfunction and integrated stress response (ISR) activation in GBM. Human GBM lines (U87, U251, T98G) and non-malignant SVG p12 astrocytes received ONC212 (0.5-80 μM) for 12-48 h. Viability was assessed by CCK-8. KATP subunit expression (Kir6.2, SUR1, CCDC51) was quantified by qRT-PCR and western blot. Mitochondrial ROS quantification, oxygen consumption rate (Seahorse XF), PERK/ATF4/CHOP activation (western blot, immunofluorescence) and apoptosis (caspase-3/7) were evaluated. KATP was modulated pharmacologically (glibenclamide, diazoxide) and via KCNJ11 (Kir6.2) siRNA. ONC212 induced time-dependent and tumour-selective cytotoxicity, with highest sensitivity observed in KATP-high U87 cells. Treatment significantly increased mitochondrial ROS, impaired oxidative phosphorylation and reduced ATP/ADP ratios, indicating bioenergetic collapse. Concurrently, ONC212 robustly activated the PERK/eIF2α/ATF4/CHOP axis and promoted ATF4 nuclear translocation. PERK inhibition attenuated both stress signalling and cytotoxicity, confirming ISR dependency. KATP inhibition enhanced ONC212-induced mitochondrial dysfunction, ISR activation and apoptosis, whereas KATP activation exerted protective effects. Importantly, KCNJ11 silencing markedly potentiated ONC212 sensitivity, amplifying ROS production, mitochondrial impairment and caspase-dependent apoptosis. KATP channel expression may regulate ONC212 responsiveness in GBM by modulating mitochondrial stress and ISR signalling. Targeting KATP channels may enhance imipridone efficacy and represents a promising strategy for metabolically guided GBM therapy. - Source: PubMed
Taskesen AhmetHacioglu Ceyhan - ATP-sensitive potassium channels regulate insulin release, with the gene encoding the Kir6.2 channel's pore subunit. The E23K variant, previously linked to type 2 diabetes (T2DM), was examined in a large Lebanese cohort to determine its relationship to diabetic retinopathy (DR) severity and glycemic control. - Source: PubMed
Publication date: 2026/07/08
Nemr RitaEchtay AkramKanabekova PerizatBauyrzhanova ZhansayaAmanzhol DanaAlmawi Wassim Y