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Kca1.1

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https://www.readbyqxmd.com/read/28630432/down-regulation-of-kca2-3-channels-causes-erectile-dysfunction-in-mice
#1
Simon Comerma-Steffensen, Attila Kun, Elise R Hedegaard, Susie Mogensen, Christian Aalkjaer, Ralf Köhler, Birgitte Mønster Christensen, Ulf Simonsen
Modulation of endothelial calcium-activated K(+) channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K(+) channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 (T/T(-Dox))) or down-regulation (KCa2.3 (T/T(+Dox))) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507328/pro-inflammatory-ca-activated-k-channels-are-inhibited-by-hydroxychloroquine
#2
María Eugenia Schroeder, Sofía Russo, Carlos Costa, Juliana Hori, Inés Tiscornia, Mariela Bollati-Fogolín, Darío S Zamboni, Gonzalo Ferreira, Ernesto Cairoli, Marcelo Hill
Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca(++)-activated K(+) conductance in THP-1 macrophages in a dose-dependent manner...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484740/expression-of-ion-channels-in-perivascular-stem-cells-derived-from-human-umbilical-cords
#3
Eunbi Kim, Won Sun Park, Seok-Ho Hong
Potassium channels, the largest group of pore proteins, selectively regulate the flow of potassium (K(+)) ions across cell membranes. The activity and expression of K(+) channels are critical for the maintenance of normal functions in vessels and neurons, and for the regulation of cell differentiation and maturation. However, their role and expression in stem cells have been poorly understood. In this study, we isolated perivascular stem cells (PVCs) from human umbilical cords and investigated the expression patterns of big-conductance Ca(2+)-activated K(+) (BKCa) and voltage-dependent K(+) (Kv) channels using the reverse transcription polymerase chain reaction...
March 2017: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/28428266/kca1-1-channels-regulate-%C3%AE-1-integrin-function-and-cell-adhesion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#4
Mark R Tanner, Michael W Pennington, Teresina Laragione, Pércio S Gulko, Christine Beeton
Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of fibroblast-like synoviocytes isolated from the synovium of patients with rheumatoid arthritis (RA-FLS). It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28396143/lethal-effects-of-an-insecticidal-spider-venom-peptide-involve-positive-allosteric-modulation-of-insect-nicotinic-acetylcholine-receptors
#5
Monique J Windley, Irina Vetter, Richard J Lewis, Graham M Nicholson
κ-Hexatoxins (κ-HXTXs) are a family of excitotoxic insect-selective neurotoxins from Australian funnel-web spiders that are lethal to a wide range of insects, but display no toxicity towards vertebrates. The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach large-conductance calcium-activated potassium (BKCa or KCa1.1) channels, but not their mammalian orthologs. Despite this potent and selective action on insect KCa1.1 channels, we found that the classical KCa1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect KCa1...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28292889/intact-colonic-kca1-1-channel-activity-in-kcnmb2-knockout-mice
#6
Casper K Larsen, Helle A Praetorius, Jens Leipziger, Mads V Sorensen
Mammalian potassium homeostasis results from tightly regulated renal and colonic excretion, which balances the unregulated dietary K(+) intake. Colonic K(+) secretion follows the pump-leak model, in which the large conductance Ca(2+)-activated K(+) channel (KCa1.1) is well established as the sole, but highly regulated apical K(+) conductance. The physiological importance of auxiliary β and γ subunits of the pore-forming α-subunit of the KCa1.1 channel is not yet fully established. This study investigates colonic K(+) secretion in a global knockout mouse of the KCa1...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28261056/proteomic-analysis-of-post-synaptic-density-fractions-from-shank3-mutant-mice-reveals-brain-region-specific-changes-relevant-to-autism-spectrum-disorder
#7
Dominik Reim, Ute Distler, Sonja Halbedl, Chiara Verpelli, Carlo Sala, Juergen Bockmann, Stefan Tenzer, Tobias M Boeckers, Michael J Schmeisser
Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome, autism spectrum disorder (ASD), and intellectual disability. Although, a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the post-synaptic protein scaffold, the molecular processes at synapses of individuals harboring SHANK3 mutations are still far from being understood. In this study, we biochemically isolated the post-synaptic density (PSD) fraction from striatum and hippocampus of adult Shank3Δ11(-/-) mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteomes (Data are available via ProteomeXchange with identifier PXD005192)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28028617/calcium-gated-k-channels-of-the-kca1-1-and-kca3-1-type-couple-intracellular-ca-2-signals-to-membrane-hyperpolarization-in-mesenchymal-stromal-cells-from-the-human-adipose-tissue
#8
Michail V Tarasov, Marina F Bystrova, Polina D Kotova, Olga A Rogachevskaja, Veronika Y Sysoeva, Stanislav S Kolesnikov
Electrogenesis in mesenchymal stromal cells (MSCs) remains poorly understood. Little is known about ion channels active in resting MSCs and activated upon MSC stimulation, particularly, by agonists mobilizing Ca(2+) in the MSC cytoplasm. A variety of Ca(2+)-gated ion channels may couple Ca(2+) signals to polarization of the plasma membrane. Here, we studied MSCs from the human adipose tissue and found that in cells responsive to ATP and adenosine with Ca(2+) transients or exhibiting spontaneous Ca(2+) oscillations, Ca(2+) bursts were associated with hyperpolarization mediated by Ca(2+)-gated K(+) channels...
February 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27973439/down-regulation-of-ca-2-activated-k%C3%A2-%C2%BA-channel-kca1-1-in-human-breast-cancer-mda-mb-453-cells-treated-with-vitamin-d-receptor-agonists
#9
Anowara Khatun, Mayu Fujimoto, Hiroaki Kito, Satomi Niwa, Takayoshi Suzuki, Susumu Ohya
Vitamin D (VD) reduces the risk of breast cancer and improves disease prognoses. Potential VD analogs are being developed as therapeutic agents for breast cancer treatments. The large-conductance Ca(2+)-activated K⁺ channel KCa1.1 regulates intracellular Ca(2+) signaling pathways and is associated with high grade tumors and poor prognoses. In the present study, we examined the effects of treatments with VD receptor (VDR) agonists on the expression and activity of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, flow cytometry, and voltage-sensitive dye imaging...
December 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27933000/in-depth-study-of-the-interaction-sensitivity-and-gating-modulation-by-pufas-on-k-channels-interaction-and-new-targets
#10
REVIEW
Cristina Moreno, Alicia de la Cruz, Carmen Valenzuela
Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K(+) ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27826710/the-action-of-smooth-muscle-cell-potassium-channels-in-the-pathology-of-pulmonary-arterial-hypertension
#11
REVIEW
Yasunobu Hayabuchi
Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference)...
January 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/27826078/participation-of-potassium-channels-in-the-antinociceptive-effect-of-docosahexaenoic-acid-in-the-rat-formalin-test
#12
Arizai Yolia Landa-Juárez, Mario I Ortiz, Gilberto Castañeda-Hernández, Aracely Evangelina Chávez-Piña
Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has shown gastroprotective, cardioprotective, neuroprotective, anti-inflammatory and antinociceptive effects in different models. However, its action mechanism is still not well-defined. Reports indicate that some PUFAs regulate potassium (K(+)) channels in ventricular myocytes of rodents. As a result, the aim of this study was to evaluate the probable participation of K(+) channels in the antinociceptive effect of DHA. The rat paw 1% formalin test was used to assess nociception and antinociception...
December 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27763639/functional-kca1-1-channels-are-crucial-for-regulating-the-proliferation-migration-and-differentiation-of-human-primary-skeletal-myoblasts
#13
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27497881/nitric-oxide-and-kir6-1-potassium-channel-mediate-isoquercitrin-induced-endothelium-dependent-and-independent-vasodilation-in-the-mesenteric-arterial-bed-of-rats
#14
Arquimedes Gasparotto Junior, Renê Dos Reis Piornedo, Jamil Assreuy, José Eduardo Da Silva-Santos
The vascular effect of flavonoid isoquercitrin was investigated in the perfused mesenteric vascular bed of rats. In preparations with functional endothelium isoquercitrin (100, 300 and 1000nmol) dose-dependently reduced the perfusion pressure by 13±2.2, 33±3.9, and 58±3.7mm Hg, respectively. Endothelium removal or inhibition of the nitric oxide synthase enzymes by l-NAME did not change the effects of 100 and 300 nmol isoquercitrin, but reduced by 30-40% the vasodilation induced by 1000 nmol isoquercitrin...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27251429/erratum-to-different-expression-of-%C3%AE-subunits-of-the-kca1-1-channel-by-invasive-and-non-invasive-human-fibroblast-like-synoviocytes
#15
Zoltán Pethő, Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S Gulko, Christine Beeton
No abstract text is available yet for this article.
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27245839/kca1-1-a-calcium-activated-potassium-channel-subunit-alpha-1-is-targeted-by-mir-17-5p-and-modulates-cell-migration-in-malignant-pleural-mesothelioma
#16
Yuen Yee Cheng, Casey M Wright, Michaela B Kirschner, Marissa Williams, Kadir H Sarun, Vladimir Sytnyk, Iryna Leshchynska, J James Edelman, Michael P Vallely, Brian C McCaughan, Sonja Klebe, Nico van Zandwijk, Ruby C Y Lin, Glen Reid
BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets...
2016: Molecular Cancer
https://www.readbyqxmd.com/read/27238271/developing-molecular-pharmacology-of-bk-channels-for-therapeutic-benefit
#17
G J Kaczorowski, M L Garcia
High conductance, calcium-activated potassium (BK) channels (KCa1.1) are important in regulating physiologic responses in many types of tissues and, as such, present opportunities for development of new therapeutic agents. Both channel agonists and inhibitors could have therapeutic utility, depending on medical application under consideration. However, characterization of molecular pharmacology of BK channels is incomplete and has been difficult to accomplish because of paucity of chemical leads that are acceptable templates for Medicinal Chemistry investigation...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27238263/protein-network-interacting-with-bk-channels
#18
H Kim, K H Oh
The large conductance, voltage- and calcium-dependent potassium BK channel, also termed BKCa, Maxi-K, KCa1.1, or SLO1, regulates a wide array of key biological processes that are mediated by calcium ions. This broad regulatory function of BK channels requires the interactions of BK channels with diverse sets of proteins that have different molecular or cellular functions. Proteins that interact with BK channels range from the auxiliary subunits of BK channels to cytoskeletal proteins responsible for BK channel trafficking and localization...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27165430/different-expression-of-%C3%AE-subunits-of-the-kca1-1-channel-by-invasive-and-non-invasive-human-fibroblast-like-synoviocytes
#19
Zoltán Pethő, Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S Gulko, Christine Beeton
BACKGROUND: Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27038377/the-modulation-of-potassium-channels-in-the-smooth-muscle-as-a-therapeutic-strategy-for-disorders-of-the-gastrointestinal-tract
#20
REVIEW
Diego Currò
Alterations of smooth muscle contractility contribute to the pathophysiology of important functional gastrointestinal disorders (FGIDs) such as functional dyspepsia and irritable bowel syndrome. Consequently, drugs that decrease smooth muscle contractility are effective treatments for these diseases. Smooth muscle contraction is mainly triggered by Ca(2+) influx through voltage-dependent channels located in the plasma membrane. Thus, the modulation of the membrane potential results in the regulation of Ca(2+) influx and cytosolic levels...
2016: Advances in Protein Chemistry and Structural Biology
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