(Dap22)-ShK, Selective blocker of Kv1.3
- Known as:
- (Dap22)-ShK, Selective blocker Kv1.3
- Catalog number:
- 13SHD001-00100
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Smartox
- Gene target:
- (Dap22)-ShK Selective blocker Kv1.3
Related products to: (Dap22)-ShK, Selective blocker of Kv1.3
Related articles to: (Dap22)-ShK, Selective blocker of Kv1.3
- Potassium (K) channels are essential transmembrane proteins that regulate ion flow, playing a critical role in regulating action potentials and neuronal transmission. Although K channel openers (agonists, K Ag) are widely used in treating neurological and psychiatric disorders, their precise mechanisms of action remain unclear. Our study explored how K channel openers might influence the expression of voltage-gated K channels (Kv) in rat brain. : Briefly, eight rats per group received intraperitoneal injections of diazoxide (Dia), chlorzoxazone (Chl), or flupirtine (Flu). Two hours post-injection, the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), dorsal hippocampus (dHIP), and ventral hippocampus (vHIP) were collected for mRNA expression analysis of various Kv. : Dia administration altered expression of in the NAc, dSTR, and vHIP, and in the PFC, dSTR, and dHIP. The mRNA levels of and changed in the NAc, dHIP, and vHIP, while expression increased in the PFC, dHIP, and vHIP of rats treated with Chl. Injection of Flu resulted in altered expression for in the NAc, dSTR, and dHIP; in the PFC, NAc, dHIP, and vHIP; in the dSTR, dHIP, and vHIP; and and in the PFC, dHIP, and vHIP. We also found dose-dependent changes. : To our knowledge, this is the first study to identify the effects of potassium channel openers on gene expression within the mesocorticolimbic and nigrostriatal dopaminergic systems. These findings reveal a novel molecular mechanism underlying the action of these drugs in the brain. Importantly, our results have broader implications for translational neuroscience, particularly in the context of repurposing FDA-approved drugs, such as diazoxide and chlorzoxazone, for the treatment of neurological disorders. - Source: PubMed
Publication date: 2025/09/26
McCoy Michael TLadenheim BruceCadet Jean LudDaiwile Atul P - Studying DNA methylation (DNAm) can provide insights into gene-regulatory mechanisms underlying attention-deficit/hyperactivity disorder (ADHD). While most DNAm studies were performed in bulk tissue, this study used statistical deconvolution to identify cell type-specific DNAm profiles, from five major blood cell types, associated with childhood ADHD symptoms. We performed meta-analyses of methylome-wide association studies (MWAS) for ADHD symptoms (age=4-16 years) in peripheral blood collected during childhood and in cord blood. The investigated cohorts included seven array-based methylation datasets assaying up to 450 K CpGs from the Pregnancy And Childhood Epigenetics Consortium (N=2 934 peripheral blood; N=2 546 cord blood) and a sequencing-based methylation dataset assaying nearly all 28 million CpGs in blood from the Great Smoky Mountain Study (GSMS; N=583). The meta-analyses resulted in methylome-wide significant (FDR<0.05) ADHD associations in CD8T cells (RPL31P11 and KCNJ5) for peripheral blood, and, in cord blood, in monocytes (PDE6B), CD8T cells (KCNA3 and HAND2), and NK cells (KIFC1). Notably, several significant sites detected in peripheral blood (RPL31P11 and KCNJ5) were also detected in cord blood. Furthermore, extended MWAS of all sites available for GSMS detected 69 and 17 additional CpGs in monocytes and granulocytes, respectively. In this first cell type-specific MWAS for ADHD, we identified DNAm associations for ADHD symptoms; some associations were seen in both peripheral blood and cord blood, suggesting potential susceptibility markers for increased ADHD risk. These findings show that cell type-specific analyses and sequencing-based approaches can increase insights into the epigenetic patterns associated with ADHD symptoms in childhood. - Source: PubMed
Publication date: 2025/10/26
Meijer MandyKlein MariekeCaramaschi DorettaClark Shaunna LCosin-Tomas MartaKoen NastassjaLu XuelingMulder Rosa HRöder Stefan WZhang YiningZilich LeaBustamente MarionaDeuschle MichaelFelix Janine FGonzález Juan RamosGražulevičiene ReginaStreit FabianWright JohnCarracedo AngelCecil Charlotte A MCorpeleijn EvaHartman Catharina AHerberth GundaHuels AnkeRelton CarolineSnieder HaroldStein Dan JSunyer JordiWitt Stephanie HZar Heather JZenclussen Ana CFranke BarbaraCopeland WilliamAberg Karolina Avan den Oord Edwin J C G - Potassium voltage-gated channels are attractive drug targets for cancer treatment. In this report, we show that K1.3 current amplitude is greater in CLL cells from refractory patients compared to CLL cells from untreated patients, further supporting a role for Kv1.3 channel as a target for refractory CLL disease. Indole-3 carbinol (I3C) is a clinically tested natural product found in edible Brassica plants. Here we show that I3C inhibits K1.3 currents in transfected HEK293 (43.9 ± 7.6 %; 50 μM I3C), Burkitt's lymphoma BL60.2 (52.2 ± 5.2 %; 10 μM) and chronic lymphocytic leukemia (CLL) (57.7 % ± 5.2; 10 μM) cells. I3C inhibition was concentration-dependent in HEK293 (IC = 54 μM; n = 3.2), BL60.2 (IC = 1.06 μM; n = 0.53) and CLL (IC = 5.2 μM; n = 0.95) cells, and the effect on K1.3 was produced in a voltage-, time- and use-dependent manner, consistent with an open state blockade mechanism. I3C also inhibited K11.1 currents, but failed to inhibit other K channels and K3.1. Interestingly I3C did not induce mitochondrial depolarization of CLL cells, suggesting that I3C only targets plasma, but not mitochondria, Kv1.3 channels. I3C and derivatives 6-methyl-I3C and 3,3'-diindolylmethane, but no other indoles, that we previously showed induced apoptosis in Burkitt's and CLL cells, also efficiently inhibited K1.3 currents. However, I3C-mediated K1.3 currents inhibition was observed in CLL cells irrespective of their sensitivity to I3C-induced cell death, thus indicating that plasma membrane K1.3 inhibition is not sufficient to induce CLL cell death. - Source: PubMed
Publication date: 2025/10/23
Baena-Nuevo MariaVera-Zambrano AlbaMartinez-Laperche CarolinaBuño IsmaelMuñoz-Calleja CeciliaValenzuela CarmenZapata Juan ManuelPerez-Chacon Gema - Kv1.3 is unique functional voltage-dependent K channel in normal and leukemic human lymphocytes. Here, we show that cell lines and primary cells of acute lymphoblastic leukemia (B-ALL) express Kv1.3 protein at high levels and that it is located at the plasma membrane. Surprisingly, and in contrast to healthy B cells, B-ALL cells lack Kv1.3 plasma membrane currents. However, B-ALL cell lines and primary B-ALL patient samples displayed a robust Ca-dependent KCa3.1 current, comparable to that in activated B cells. The importance of the present finding for further development of antileukemic chemotherapeutic strategies is that the lack of one of the two principal lymphocyte K currents, which are partly redundant in their function, could render B-ALL cells more vulnerable to treatments targeting the remaining KCa3.1 current. - Source: PubMed
Publication date: 2025/10/08
Torres-López LilianaOlivas-Aguirre MiguelCastellanos-Martínez RamónJiménez-Camacho Karina ElizabethPelayo RosanaDobrovinskaya OxanaSchnoor MichaelPottosin Igor - Genetic studies have investigated the association of genetic variants with Immunoglobulin G4-related disease (IgG4-RD). In this study, we summarize the results of genetic association in IgG4-RD. - Source: PubMed
Publication date: 2025/10/13
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