KCNMA1 polyclonal antibody
- Known as:
- KCNMA1 pab (anti-)
- Catalog number:
- PAB15639
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Abno
- Gene target:
- KCNMA1 polyclonal antibody
Related genes to: KCNMA1 polyclonal antibody
- Gene:
- KCNMA1 NIH gene
- Name:
- potassium calcium-activated channel subfamily M alpha 1
- Previous symbol:
- SLO
- Synonyms:
- KCa1.1, mSLO1
- Chromosome:
- 10q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-15
- Date modifiied:
- 2016-10-05
Related products to: KCNMA1 polyclonal antibody
Related articles to: KCNMA1 polyclonal antibody
- Large-conductance Ca-activated potassium (BK) channels have been implicated in glioblastoma progression and oxidative stress; however, their contribution to the cellular response to ionizing radiation remains poorly understood. Potassium channels represent attractive therapeutic targets because their activity can be modulated pharmacologically using selective inhibitors or genetically by gene silencing (siRNA) or gene knockout (CRISPR/Cas9). Here, we investigated whether genetic inhibition of BK modulates the DNA damage response of human glioblastoma cells following electron ultra-high dose rate (UHDR) irradiation. - Source: PubMed
Publication date: 2026/09/22
Maliszewska-Olejniczak KamilaFryc MichałKustra AgataWiktorska KatarzynaLenartowicz-Gasik AleksandraSoroka WojciechRzadkiewicz JacekŻochowska MonikaKulawiak BoguszBednarczyk Piotr - Objective This study aims to identify immune-related key genes in sepsis using transcriptomic analysis and machine learning, and to explore the role of dexmedetomidine (DEX) in sepsis regulation through these genes. Methods The transcriptomic dataset GSE9960 related to sepsis was obtained from the gene expression omnibus (GEO) database. Differential expression analysis and visualization were performed using the limma and ggplot2 packages in R 4.5.1. DEX targets were collected from the comparative toxicogenomics database (CTD), SwissTargetPrediction, and GeneCards databases, followed by integration and removal of duplicates to obtain the overall DEX target set. Immune-related targets were also retrieved from the GeneCards database. The DEX targets, sepsis-related targets, and immune-related targets were intersected to identify DEX-targeted immune-related sepsis targets. Key targets were screened using least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms, and the overlapping targets were further identified as core DEX-targeted immune targets in sepsis. Immune infiltration was evaluated using the CIBERSORT algorithm combined with Spearman correlation analysis, and the correlations between core targets and immune cell populations were further investigated. In vitro, a sepsis cell model was established by lipopolysaccharide (LPS) stimulation of the human monocyte cell line THP-1. Target gene knockdown or overexpression was achieved through gene transfection. Western blot analysis was performed to evaluate the effects of DEX treatment and potassium calcium-activated channel subfamily M α1 (KCNMA1) regulation on sepsis-related proteins and inflammatory cytokine levels. Results Sepsis-related dataset GSE9960 exhibited significant differential expression. After integrating and removing duplicates among sepsis-, immune-, and DEX-related targets, 25 key immune targets of DEX against sepsis were identified. LASSO and RF analyses further screened three core targets. Immune infiltration analysis showed that these core targets were significantly associated with plasma cells, neutrophils, and resting memory CD4 T cells. Since KCNMA1 exhibited the most prominent upregulation and the greatest differential expression, it was selected for further experimental validation. The results demonstrated that DEX treatment reduced the expression of sepsis-related proteins, including KCNMA1, cyclin B2 (CCNB2), and NEDD4 E3 ubiquitin protein ligase (NEDD4), and suppressed inflammatory cytokine levels by downregulating KCNMA1. Conclusion DEX suppresses the development of sepsis by downregulating KCNMA1 expression. - Source: PubMed
Chen XiaofengChen MingdiLi FujunChen Meifeng - Slo1 channels regulate key electrochemical signaling events in a variety of excitable and nonexcitable cells. Here, we have investigated the mechanisms by which distinct small molecules inhibit human Slo1 (hSlo1) channel activity using single-particle cryo-EM, liposome flux, and toxin-binding assays. We find that unlike classical permeation blockers like scorpion toxins, indole diterpene (ID) class of fungal mycotoxins, paxilline and penitrem A, are ensconced in a binding pocket, deep within the putatively closed hSlo1 pore and sterically restrict its opening. Binding of paxilline to its gating inhibition site dramatically slows dissociation of a fluorescent charybdotoxin derivative, via an allosteric mechanism that likely involves a key residue on the S5 helix (W246). Although four paxilline molecules may concurrently engage the hSlo1 pore, binding of <4 molecules is sufficient for efficacious inhibition of channel opening but inefficient at arresting toxin dissociation. We also find evidence that under divalent and ID free conditions, the ID binding pocket of hSlo1 is occluded by lipids that extend into the hSlo1 pore lumen through interhelical crevices that become constricted in the divalent bound open state. These lipids may not only competitively regulate ID binding but also tune the energetics of channel gating, sterically or by altering the hydration state of the pore vestibule. Our study provides a framework to understand fundamental Slo1 gating mechanisms and aid future developments of therapeutically beneficial small molecule Slo1 inhibitors. - Source: PubMed
Publication date: 2026/09/14
Kallure Gopal SPal KamalenduPrather Gabriel WChowdhury Sandipan - is 1 of 30 species of licorice, which has been prescribed for centuries for a wide range of ailments and conditions. In particular, licorice root extract, as well as its main isoflavonoid constituent, glabridin, has been used to treat a variety of respiratory diseases, ranging from infection to asthma. As glabridin has been shown to modulate the activity of ion channels in other tissues, we determined the effect of glabridin on K and Cl secretion across primary human bronchial epithelial cells (HBEs), as these may represent therapeutic targets. Glabridin stimulated BK-dependent transepithelial potassium secretion across HBEs. In contrast, the glabridin derivative, vutiglabridin, failed to stimulate K secretion and inhibited the glabridin-dependent K secretory current. Whole cell patch-clamp studies on HEK cells expressing BK demonstrate that glabridin activates, whereas vutiglabridin inhibits, BK. We further demonstrate glabridin inhibits forskolin-mediated transepithelial Cl secretion across HBEs, whereas vutiglabridin has little effect. Using Fisher rat thyroid (FRT) cells stably expressing either wild-type (FRT-WT) or F508del CFTR (FRT-F508del), we demonstrate glabridin neither potentiates WT CFTR nor corrects F508del CFTR. In contrast, whole cell patch-clamp studies demonstrate glabridin inhibits KCa3.1 stably expressed in HEK cells. We previously demonstrated a role for KCa3.1 in forskolin-mediated Cl secretion across HBEs, likely explaining the inhibition of Cl secretion observed. In summary, we show that glabridin both stimulates BK-dependent K secretion and inhibits cAMP-mediated Cl secretion across HBEs. These findings support a role for BK in the therapeutic effects of glabridin in airway. We demonstrate for the first time that the natural isoflavone, glabridin, stimulates transepithelial K secretion and inhibits forskolin-mediated Cl secretion across primary human bronchial epithelial cells (HBEs). We demonstrate that these effects are due to the activation of BK and inhibition of KCa3.1, respectively. Furthermore, glabridin does not potentiate wild-type (WT) or correct F508del CFTR. In contrast, the glabridin derivative, vutiglabridin, inhibits BK and is antagonistic to the action of glabridin in HBEs. - Source: PubMed
Publication date: 2026/09/02
Kolski-Andreaco AaronSembrat JohnButterworth Michael BDevor Daniel C - Circulating vasoactive steroids including estrogens, androgens, progesterone, and bile acids modulate the activity of voltage/Ca-gated, big conductance potassium (BK) channels, an action that requires regulatory BK β subunits. In contrast, pregnenolone at local/therapeutic concentrations has recently been shown to modulate BK channel activity in absence of such subunits. The site and mechanism of pregnenolone action remain unknown. Thus, we decided to test the hypothesis that BK channel-forming α subunits (slo1 proteins encoded by KCNMA1 or Slo1 in mammals) contain a specific residue(s) that recognizes pregnenolone and mediates modulation of smooth muscle BK channel activity and diameter of cerebral arteries by this steroid. We used microscale thermophoresis to demonstrate that pregnenolone at local/therapeutic concentrations binds to slo1 proteins (K=3.5 μM); these concentrations were reported to inhibit BK channel activity and decrease cerebral artery diameter. Based on a slo1 cryo-EM structure (PDB 6V38) computational modeling identified Tyr450, Hys409 and Asp896 as participants in pregnenolone recognition, with hydrogen-arene interactions between steroid and Tyr450. Consistently, slo1Y450F proteins failed to bind pregnenolone. Following heterologous expression, this mutant was resistant to pregnenolone-induced inhibition, an action that was coupled to Ca-driven gating and enabled by the RCK1 high-affinity Ca-binding site. In contrast to their wild-type counterparts, middle cerebral arteries from Kcnma1 Y450F knock-in mice failed to constrict to pregnenolone, whether probed ex vivo or in vivo. Thus, metabolic, circulating, or endothelial factors cannot override pregnenolone cerebrovascular action, which mainly results from direct interaction with Tyr450 within the proximal CRAC motif in the slo1 cytosolic tail domain. Our study provides a new paradigm in vasoactive steroid-BK channel interactions that can be used in developing pharmacophores/new agents to replace/regulate pregnenolone effects in clinical scenarios, and underscores that CRAC motifs may mediate ionotropic receptor regulation by steroids other than cholesterol. - Source: PubMed
Publication date: 2026/08/23
North Kelsey CThapa ShiwaniMysiewicz Steven CShaw Andrew AHomanics Gregg EBukiya Anna NDopico Alex M