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https://www.readbyqxmd.com/read/29773995/hypoxia-reoxygenation-of-rat-renal-arteries-impairs-vasorelaxation-via-modulation-of-endothelium-independent-sgc-cgmp-pkg-signaling
#1
Diana Braun, Christa Zollbrecht, Stefanie Dietze, Rudolf Schubert, Stefan Golz, Holger Summer, Pontus B Persson, Mattias Carlström, Marion Ludwig, Andreas Patzak
Ischemia/reperfusion injury holds a key position in many pathological conditions such as acute kidney injury and in the transition to chronic stages of renal damage. We hypothesized that besides a reported disproportional activation of vasoconstrictor response, hypoxia/reoxygenation (H/R) adversely affects endothelial dilatory systems and impairs relaxation in renal arteries. Rat renal interlobar arteries were studied under isometric conditions. Hypoxia was induced by application of 95% N2 , 5% CO2 for 60 min to the bath solution, followed by a 10 min period of reoxygenation (95% O2 , 5% CO2 )...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29753043/ska-31-an-activator-of-endothelial-ca-2-activated-k-channels-evokes-robust-vasodilation-in-rat-mesenteric-arteries
#2
Rayan Khaddaj-Mallat, Cini Mathew John, Andrew P Braun
It is now well recognized that endothelial KCa2.3 and KCa3.1 channel activities contribute to dilation of resistance arteries via endothelium-mediated hyperpolarization and vascular smooth muscle relaxation. In this study, we have investigated the functional effect of the KCa channel activator SKA-31 in third order rat mesenteric arteries using arterial pressure myography. Isolated arteries were cannulated, pressurized intraluminally to 70mmHg at 36°C and then constricted with 1μM phenylephrine. Acute bath exposure to SKA-31 evoked a robust and reversible inhibition of developed tone (IC50 = 0...
May 9, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29692361/a-defect-in-kca3-1-channel-activity-limits-the-ability-of-cd8-t-cells-from-cancer-patients-to-infiltrate-an-adenosine-rich-microenvironment
#3
Ameet A Chimote, Andras Balajthy, Michael J Arnold, Hannah S Newton, Peter Hajdu, Julianne Qualtieri, Trisha Wise-Draper, Laura Conforti
The limited ability of cytotoxic T cells to infiltrate solid tumors hampers immune surveillance and the efficacy of immunotherapies in cancer. Adenosine accumulates in solid tumors and inhibits tumor-specific T cells. Adenosine inhibits T cell motility through the A2A receptor (A2A R) and suppression of KCa3.1 channels. We conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8+ T cells from head and neck squamous cell carcinoma (HNSCC) patients...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29621746/crocin-improves-the-endothelial-function-regulated-by-kca3-1-through-erk-and-akt-signaling-pathways
#4
Huike Yang, Xuemei Li, Yang Liu, Xinlei Li, Xiaodong Li, Mengnan Wu, Xiaohong Lv, Chun Chunhua, Xuansheng Ding, Yafang Zhang
BACKGROUND/AIMS: Based on the protective effect of crocin against cardiovascular diseases, we hypothesize that crocin could improve endothelial function through activating the eNOS(endothelial nitric oxide synthase) /NO pathway and/or the intermediate-conductance Ca2+-activated K+ channels (KCa3.1). METHODS: In this study, rat aortic rings were used to assess the regulatory effect of crocin on vascular tone and nitric oxide, prostacyclin, and KCa3.1, all endothelial vasodilators, were analyzed for effects by crocin...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29577810/pharmacologic-targeting-of-endothelial-ca-2-activated-k-channels-a-strategy-to-improve-cardiovascular-function
#5
Cini Mathew John, Rayan Khaddaj Mallat, Grace George, Taeyeob Kim, Ramesh C Mishra, Andrew P Braun
Endothelial small and intermediate-conductance, Ca2+ -activated K+ channels (KCa2.3 and KCa3.1, respectively) play an important role in the regulation of vascular function and systemic blood pressure. Growing evidence indicates that they are intimately involved in agonist-evoked vasodilation of small resistance arteries throughout the circulation. Small molecule activators of KCa2.x and 3.1 channels, such as SKA-31, can acutely inhibit myogenic tone in isolated resistance arteries, induce effective vasodilation in intact vascular beds, such as the coronary circulation, and acutely decrease systemic blood pressure in vivo...
March 26, 2018: Channels
https://www.readbyqxmd.com/read/29574723/calcium-dependent-potassium-channels-control-proliferation-of-cardiac-progenitor-cells-and-bone-marrow-derived-mesenchymal-stem-cells
#6
Patrick Vigneault, Patrice Naud, Xiaoyan Qi, Jiening Xiao, Louis Villeneuve, Darryl R Davis, Stanley Nattel
Endogenous c-Kit+ cardiac progenitor cells (eCPCs) and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are being developed for cardiac regenerative therapy, but a better understanding of their physiology is needed. Here, we addressed the unknown functional role of ion-channels in freshly-isolated eCPCs and expanded BM-MSCs using patch-clamp, microfluorometry and confocal microscopy. Isolated c-Kit+ eCPCs were purified from dog hearts by immunomagnetic selection. Ion-currents were barely detectable in freshly-isolated c-Kit+ eCPCs with intracellular calcium (Ca2+ i ) buffered...
March 25, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29554088/kca3-1-ion-channel-a-novel-therapeutic-target-for-corneal-fibrosis
#7
Govindaraj Anumanthan, Suneel Gupta, Michael K Fink, Nathan P Hesemann, Douglas K Bowles, Lindsey M McDaniel, Maaz Muhammad, Rajiv R Mohan
Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3...
2018: PloS One
https://www.readbyqxmd.com/read/29425253/the-kca3-1-blocker-tram34-reverses-renal-damage-in-a-mouse-model-of-established-diabetic-nephropathy
#8
Chunling Huang, Ling Zhang, Ying Shi, Hao Yi, Yongli Zhao, Jason Chen, Carol A Pollock, Xin-Ming Chen
Despite optimal control of hyperglycaemia, hypertension, and dyslipidaemia, the number of patients with diabetic nephropathy (DN) continues to grow. Strategies to target various signaling pathways to prevent DN have been intensively investigated in animal models and many have been proved to be promising. However, targeting these pathways once kidney disease is established, remain unsatisfactory. The clinical scenario is that patients with diabetes mellitus often present with established kidney damage and need effective treatments to repair and reverse the kidney damage...
2018: PloS One
https://www.readbyqxmd.com/read/29388859/inhibitory-effects-of-candesartan-on-kca3-1-potassium-channel-expression-and-cell-culture-and-proliferation-in-peripheral-blood-cd4-t-lymphocytes-in-kazakh-patients-with-hypertension-from-the-xinjiang-region
#9
Hui Li, Jun-Ling Zhao, Yuan-Ming Zhang, Su-Xia Han
BACKGROUND AND AIM: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China. METHODS: Flow cytometry technology was used for T-lymphocyte subtype analysis...
2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29365273/p2y-receptor-regulation-of-k2p-channels-that-facilitate-k-secretion-by-human-mammary-epithelial-cells
#10
Yotesawee Srisomboon, Nathan A Zaidman, Peter J Maniak, Chatsri Deachapunya, Scott M O'Grady
The objective of this study was to determine the molecular identity of ion channels involved in K+ secretion by the mammary epithelium and to examine their regulation by purinoceptor agonists. Apical membrane voltage clamp experiments were performed on human mammary epithelial cells where the basolateral membrane was exposed to the pore-forming antibiotic amphotericin B dissolved in a solution with intracellular-like ionic composition. Addition of the Na+ channel inhibitor benzamil reduced the basal current, consistent with inhibition of Na+ uptake across the apical membrane whereas the KCa 3...
January 24, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29348824/k-ca-3-1-channel-inhibition-leads-to-an-icam-1-dependent-increase-of-cell-cell-adhesion-between-a549-lung-cancer-and-hmec-1-endothelial-cells
#11
Etmar Bulk, Nadzeya Kramko, Ivan Liashkovich, Felix Glaser, Hermann Schillers, Hans-Joachim Schnittler, Hans Oberleithner, Albrecht Schwab
Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year survival rate is only 15%. We could recently show that the Ca2+ sensitive K+ channel KCa 3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC) cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients die of metastases, we investigated whether KCa 3.1 channels contribute to poor patient prognosis by regulating distinct steps of the metastatic cascade. We investigated the extravasation of NSCLC cells and focused on their adhesion to endothelial cells and on transendothelial migration...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334762/altered-redox-state-modulates-endothelial-k-ca-2-3-and-k-ca-3-1-levels-in-normal-pregnancy-and-preeclampsia
#12
Shinkyu Choi, Ji Aee Kim, Hai-Yan Li, Sae-Jin Lee, Ye Seon Seok, Tae Hun Kim, Ki-Hwan Han, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh
AIMS: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial KCa 2.3 and KCa 3.1 (KCa s) play an important role in vasodilation, and KCa s levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated KCa s expression modulation during NP and PE. RESULTS: Human uterine microvascular endothelial cells were incubated in serum from normal nonpregnant women (n = 13) and women with NP (n = 24) or PE (n = 15), or in vascular endothelial growth factor (VEGF), oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17β (E2 )-containing medium for 24 h...
February 26, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29321510/a-model-of-human-lung-fibrogenesis-for-the-assessment-of-anti-fibrotic-strategies-in-idiopathic-pulmonary-fibrosis
#13
Katy M Roach, Amanda Sutcliffe, Laura Matthews, Gill Elliott, Chris Newby, Yassine Amrani, Peter Bradding
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa 3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa 3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29246953/ca-2-dependent-regulation-of-nfatc1-via-kca3-1-in-inflammatory-osteoclastogenesis
#14
Eva M Grössinger, Mincheol Kang, Laura Bouchareychas, Ritu Sarin, Dominik R Haudenschild, Laura N Borodinsky, Iannis E Adamopoulos
In inflammatory arthritis, the dysregulation of osteoclast activity by proinflammatory cytokines, including TNF, interferes with bone remodeling during inflammation through Ca2+ -dependent mechanisms causing pathological bone loss. Ca2+ -dependent CREB/c-fos activation via Ca2+ -calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast-specific genes via NFATc1, which facilitate bone resorption. In leukocytes, Ca2+ regulation of NFAT-dependent gene expression oftentimes involves the activity of the Ca2+ -activated K+ channel KCa3...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29242028/blockade-of-kca3-1-a-novel-target-to-treat-tgf-%C3%AE-1-induced-conjunctival-fibrosis
#15
Govindaraj Anumanthan, Philip J Wilson, Ratnakar Tripathi, Nathan P Hesemann, Rajiv R Mohan
Postoperative conjunctival fibrosis is common in patients after glaucoma filtration surgery. The calcium activated potassium (KCa3.1) channel has been shown to inhibit fibrosis in many non-ocular tissues. However, its potential in treating ocular fibrosis remains unknown. We tested the anti-fibrotic potential of TRAM34, a selective blocker of KCa3.1 channel, in treating conjunctival fibrosis. Primary human conjunctival fibroblast (HCF) cultures derived from donor tissues. Myofibroblasts causing conjunctival fibrosis were generated by growing HCFs in the presence of TGFβ1 for 72 h...
February 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29194075/cutaneous-angiosarcoma-update-on-biology-and-latest-treatment
#16
Yoshihiro Ishida, Atsushi Otsuka, Kenji Kabashima
PURPOSE OF REVIEW: The present review aims to provide readers with the latest updates on the biology and clinical management of cutaneous angiosarcoma (cAS). RECENT FINDINGS: The genomic alteration of cAS is heterogeneous. Mutations are enriched in the mitosis-activated kinase (MAPK) pathway. Functional analysis has identified molecules that may serve as potential markers and therapeutic targets of angiosarcoma. These molecules include survivin, HSP90, FOXM1, miR-497-5p, KCa3...
March 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29167619/exenatide-inhibits-the-k-ca-3-1-channels-of-aortic-vascular-smooth-muscle-in-diabetic-rats
#17
Peng Dong, Minglong Liu, Chaofeng Liu
Background: KCa 3.1 ion channels play an important role during atherosclerosis. We aimed to investigate the effect of exenatide on KCa 3.1 expression in aortic vascular smooth muscle cells (VSMCs) of diabetic rats. Methods: Sprague-Dawley rats were randomly divided into normal control (NC), diabetes model (DM), and exenatide treatment (ET) groups. Hematoxylin and eosin and α-actin immunohistochemical staining were used to detect changes in rat aortic vascular smooth muscle...
November 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/29161243/the-combined-activation-of-k-ca-3-1-and-inhibition-of-k-v-11-1-herg1-currents-contribute-to-overcome-cisplatin-resistance-in-colorectal-cancer-cells
#18
Serena Pillozzi, Massimo D'Amico, Gianluca Bartoli, Luca Gasparoli, Giulia Petroni, Olivia Crociani, Tiziano Marzo, Angela Guerriero, Luigi Messori, Mirko Severi, Roberto Udisti, Heike Wulff, K George Chandy, Andrea Becchetti, Annarosa Arcangeli
BACKGROUND: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K+ channel modulators on colorectal cancer (CRC) cells. METHODS: The functional expression of Ca2+ -activated (KCa 3.1, also known as KCNN4) and voltage-dependent (Kv 11...
January 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29155298/mechanisms-of-l-alpha-lysophosphatidylinositol-induced-relaxation-in-human-pulmonary-arteries
#19
Olga Karpińska, Marta Baranowska-Kuczko, Barbara Malinowska, Monika Kloza, Magdalena Kusaczuk, Agnieszka Gęgotek, Paweł Golec, Irena Kasacka, Hanna Kozłowska
AIMS: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs). MAIN METHODS: Functional studies were performed in isolated hPAs using organ bath technique. The expression of GPR55 in hPAs and bronchioles was determined by real-time qPCR, Western blot analysis, and immunohistochemistry...
January 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29098165/a-trpm4-inhibitor-9-phenanthrol-inhibits-glucose-and-glucagon-like-peptide-1-induced-insulin-secretion-from-rat-islets-of-langerhans
#20
Zuheng Ma, Anneli Björklund, Md Shahidul Islam
Pancreatic β -cells express several ion channels of the transient receptor potential family, which play important roles in mediating the stimulus-secretion coupling. One of these channels, the TRPM4 is a Ca2+ -activated monovalent cation channel. This channel is inhibited by 9-phenanthrol, which also inhibits the TMEM16a Cl- channel, and activates the Ca2+ -activated K+ channel, Kca 3.1. The net effects of ion-channel modulation by 9-phenantherol on the insulin secretion remain unclear. We tested the effects of 9-phenanthrol on glucose- and GLP-1-induced insulin secretion from isolated rat islets in static incubations...
2017: Journal of Diabetes Research
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