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https://www.readbyqxmd.com/read/28054347/ano1-in-intramuscular-interstitial-cells-of-cajal-plays-a-key-role-in-the-generation-of-slow-waves-and-tone-in-the-internal-anal-sphincter
#1
C A Cobine, E E Hannah, M H Zhu, H E Lyle, J R Rock, K M Sanders, S M Ward, K D Keef
The mechanism underlying tone generation in the internal anal sphincter (IAS) is controversial. We examined the hypothesis that tone depends upon generation of electrical slow waves (SWs) initiated in intramuscular interstitial cells of Cajal (ICC-IM) by activation of Ca(2+) -activated Cl(-) channels (encoded by Ano1) and voltage-dependent L-type Ca(2+) channels (encoded by Cacna1c). Phasic contractions and tone in the IAS were nearly abolished by ANO1 and CavL antagonists. ANO1 antagonists also abolished SWs as well as transient depolarizations that persisted after addition of CavL antagonists...
January 4, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28054154/interstitial-cell-modulation-of-pyeloureteric-peristalsis-in-the-mouse-renal-pelvis-examined-using-fibsem-tomography-and-calcium-indicators
#2
Hikaru Hashitani, Michael J Nguyen, Haruka Noda, Retsu Mitsui, Ryuhei Higashi, Keisuke Ohta, Kei-Ichiro Nakamura, Richard J Lang
Typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) and interstitial cells (ICs) within the pacemaker region of the mouse renal pelvis were examined using focused ion beam scanning electron (FIB SEM) tomography, immunohistochemistry and Ca(2+) imaging. Individual cells within 500-900 electron micrograph stacks were volume rendered and associations with their neighbours established. 'Ribbon-shaped', Ano1 Cl(-) channel immuno-reactive ICs were present in the adventitia and the sub-urothelial space adjacent to the TSMC layer...
January 4, 2017: Pflügers Archiv: European Journal of Physiology
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
#3
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...
December 27, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28004965/restoration-of-density-of-interstitial-cells-of-cajal-in-the-jejunum-of-diabetic-rats-after-quercetin-supplementation
#4
Flávia Cristina Vieira Frez, Juliana Vanessa Martins Colombo Perles, David Robert Linden, Simon John Gibbons, Heber Amilcar Martins, Débora Almeida Brito Romualdo, Sara Raquel de Souza, Gleison Daion Piovezana Bossolani, Jacqueline Nelisis Zanoni
BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal motility in the gastrointestinal tract. Depletion of ICC has been associated with diabetic gastroenteropathy. PURPOSE: To determine the effect of quercertin supplementation on anoctamin-1 (Ano1) immunoreactive ICC in the myenteric region (ICC-MY) and deep muscular plexus (ICC-DMP) in the jejunum of diabetic rats. METHODS: Thirty-two 90-day-old male Wistar rats were distributed into the following groups: normoglycemic (C), normoglycemic supplemented with quercetin (CQ; 40 mg daily), diabetic (D), and diabetic supplemented with quercetin (DQ; 40 mg daily)...
December 22, 2016: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/27997763/the-stem-cell-growth-factor-receptor-kit-is-not-expressed-on-interstitial-cells-in-bladder
#5
Thomas Gevaert, Dirk De Ridder, Els Vanstreels, Dirk Daelemans, Wouter Everaerts, Frank Van Der Aa, Isabel Pintelon, Jean-Pierre Timmermans, Tania Roskams, Clara Steiner, Jochen Neuhaus
The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT(+) ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27979828/conditional-genetic-deletion-of-ano1-in-interstitial-cells-of-cajal-impairs-ca2-transients-and-slow-waves-in-adult-mouse-small-intestine
#6
John Malysz, Simon J Gibbons, Siva A Saravanaperumal, Peng Du, Seth T Eisenman, Chike Cao, Uhtaek Oh, Dieter Saur, Sabine Klein, Tamas Ordog, Gianrico Farrugia
Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit(+) electrical pacemakers that express the Ano1/TMEM16A Ca(2+)-activated Cl(-) channel, whose functions in the GI tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. Kit(CreERT2/+);Ano1(Fl/Fl) mice were treated with tamoxifen or vehicle, and small intestines (mucosa-free) examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knock-outs (cKOs) compared to vehicle-treated controls...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932986/role-of-quercetin-in-modulating-chloride-transport-in-the-intestine
#7
Bo Yu, Yu Jiang, Lingling Jin, Tonghui Ma, Hong Yang
Epithelial chloride channels provide the pathways for fluid secretion in the intestine. Cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs) are the main chloride channels in the luminal membrane of enterocytes. These transmembrane proteins play important roles in many physiological processes. In this study, we have identified a flavonoid quercetin as a modulator of CaCC chloride channel activity. Fluorescence quenching assay showed that quercetin activated Cl(-) transport in a dose-dependent manner, with EC50 ~37 μM...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27875260/the-presence-and-role-of-interstitial-cells-of-cajal-in-the-proximal-intestine-of-shorthorn-sculpin-myoxocephalus-scorpius
#8
Jeroen Brijs, Grant W Hennig, Anna-Maria Kellermann, Michael Axelsson, Catharina Olsson
Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation due to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically-driven component of gastrointestinal motility patterns in fish likely also involves ICC, however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius)...
November 10, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27860832/anoctamins-tmem16-proteins-chloride-channels-flirting-with-lipids-and-extracellular-vesicles
#9
Jarred M Whitlock, H Criss Hartzell
Anoctamin/TMEM16 proteins exhibit diverse functions in cells throughout the body and are implicated in several human diseases. Although the founding members ANO1 (TMEM16A) and ANO2 (TMEM16B) are Ca(2+)-activated Cl(-) channels, most ANO paralogs are Ca(2+)-dependent phospholipid scramblases that serve as channels facilitating the movement (scrambling) of phospholipids between leaflets of the membrane bilayer. Phospholipid scrambling significantly alters the physical properties of the membrane and its landscape and has vast downstream signaling consequences...
November 16, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27859335/extracellular-protons-enable-activation-of-the-calcium-dependent-chloride-channel-tmem16a-ano1
#10
Silvia Cruz-Rangel, José J De Jesus-Pérez, Iván A Aréchiga-Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore forming subunit of a Ca(2+) -dependent Cl(-) channel (CaCC), is activated by direct, voltage-dependent, binding of intracellular Ca(2+) . Endogenous CaCCs are regulated by extracellular protons; however, the molecular basis of such regulation remains unidentified. Here, we evaluated the effects of different extracellular proton concentrations ([H(+) ]o ) on mouse TMEM16A expressed in HEK-293 cells using whole-cell and inside-out patch clamp recordings. We found that increasing the [H(+) ]o from 10(-10) to 10(-5...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27832662/effects-of-exogenous-interleukin-9-on-the-growth-proliferation-and-activity-of-interstitial-cells-of-cajal-cultured-in-vitro
#11
Lei Huang, Baofeng Du, Yaoyao Gong, Hairong Xu, Jia Lu, Xinmin Si
OBJECTIVES: To evaluate the role of exogenous interleukin-9 (IL-9) in the growth, proliferation and activity of interstitial cells of Cajal (ICCs) cultured in vitro, and to assess its role in maintaining the functions of ICCs. METHODS: ICCs of murine gastric antrum were isolated and cultured in vitro. ICCs were identified with c-Kit and ANO1 immunofluorescent antibodies. Both fluorescence microscope and confocal microscopy were used to observe the effects of IL-9 on the growth, proliferation and activity of ICCs in cultured in vitro...
2016: Digestion
https://www.readbyqxmd.com/read/27822608/expression-of-anoctamins-in-retinal-pigment-epithelium-rpe
#12
Rainer Schreiber, Karl Kunzelmann
The anoctamin (ANO, TMEM16) family of Ca(2+)-activated Cl(-) channels consists of ten members with different cellular functions (ANO1-10). ANO1 is a Ca(2+)-activated Cl(-) channel in secretory epithelial cells of exocrine pancreas, salivary glands, or enterocytes. Expression of ANO1 also promotes cell proliferation and migration of tumor cells. ANO6 is essential for Ca(2+)-dependent scrambling of membrane phospholipids in platelets, red blood cells, and lymphocytes. ANO10 modulates Ca(2+) signals in macrophages and has a role in cerebellar ataxia and other neurological disorders...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27799301/anoctamin-6-contributes-to-cl-secretion-in-accessory-cholera-enterotoxin-ace-stimulated-diarrhea-an-essential-role-for-phosphatidylinositol-4-5-bisphosphate-pip2-signaling-in-cholera
#13
Joydeep Aoun, Mikio Hayashi, Irshad Ali Sheikh, Paramita Sarkar, Tultul Saha, Priyanka Ghosh, Rajsekhar Bhowmick, Dipanjan Ghosh, Tanaya Chatterjee, Pinak Chakrabarti, Manoj K Chakrabarti, Kazi Mirajul Hoque
Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea. However, the signaling mechanism and specific type of Cl(-) channel activated by Ace are still unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane, which was inhibited by classical CaCC blockers. Surprisingly, an Ace-elicited rise of current was neither affected by ANO1 (TMEM16A)-specific inhibitor T16A(inh)-AO1(TAO1) nor by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker, CFTR inh-172...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27750372/copy-number-gain-of-11q13-3-genes-associates-with-pathological-stage-in-hypopharyngeal-squamous-cell-carcinoma
#14
Samuel B Pattle, Natasa Utjesanovic, Athena Togo, Lucy Wells, Brendan Conn, Hannah Monaghan, Elizabeth Junor, Ingolfur Johannessen, Kate Cuschieri, Simon Talbot
Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q-PIK3CA, TP63; 11q13...
October 17, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27742704/na-k-cl-cotransporter-nkcc-maintains-the-chloride-gradient-to-sustain-pacemaker-activity-in-interstitial-cells-of-cajal
#15
Mei Hong Zhu, Tae Sik Sung, Masaaki Kurahashi, Lauren E O'Kane, Kate O'Driscoll, Sang Don Koh, Kenton M Sanders
Interstitial cells of Cajal (ICC) generate electrical slow waves by coordinated openings of ANO1 channels, a Ca(2+)-activated Cl(-) (CaCC) conductance. Efflux of Cl(-) during slow waves must be significant, as there is high current density during slow-wave currents and slow waves are of sufficient magnitude to depolarize the syncytium of smooth muscle cells and PDGFRα(+) cells to which they are electrically coupled. We investigated how the driving force for Cl(-) current is maintained in ICC. We found robust expression of Slc12a2 (which encodes an Na(+)-K(+)-Cl(-) cotransporter, NKCC1) and immunohistochemical confirmation that NKCC1 is expressed in ICC...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27732935/inhibition-of-calcium-activated-chloride-channel-ano1-suppresses-proliferation-and-induces-apoptosis-of-epithelium-originated-cancer-cells
#16
Lizhao Guan, Yan Song, Jian Gao, Jianjun Gao, KeWei Wang
ANO1, a calcium-activated chloride channel, has been reported to be amplified or overexpressed in tissues of several cancers. However, reports on its roles in tumor progression obtained from cancer cell lines are inconsistent, suggesting that the role of ANO1 in tumorigenesis is likely dependent on either its expression level or cell-type expressing ANO1. To investigate the biological roles of ANO1 in different tumor cells, we, in this study, selected several cancer cell lines and a normal HaCaT cell line with high expression levels of ANO1, and examined the function of ANO1 in these cells using approaches of lentiviral knockdown and pharmacological inhibition...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27721237/store-operated-ca2-entry-regulates-ca2-activated-chloride-channels-and-eccrine-sweat-gland-function
#17
Axel R Concepcion, Martin Vaeth, Larry E Wagner, Miriam Eckstein, Lee Hecht, Jun Yang, David Crottes, Maximilian Seidl, Hyosup P Shin, Carl Weidinger, Scott Cameron, Stuart E Turvey, Thomas Issekutz, Isabelle Meyts, Rodrigo S Lacruz, Mario Cuk, David I Yule, Stefan Feske
Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27689413/estrogens-exacerbate-nociceptive-pain-via-upregulation-of-trpv1-and-ano1-in-trigeminal-primary-neurons-of-female-rats
#18
Kazuaki Yamagata, Mitsutaka Sugimura, Miki Yoshida, Shinichi Sekine, Akiyo Kawano, Aiko Oyamaguchi, Hiroharu Maegawa, Hitoshi Niwa
Several trigeminal pain disorders show sex differences, and high levels of estrogens may underlie these differences. The interaction between transient receptor potential vanilloid 1 (TRPV1) and anoctamin 1 (ANO1) plays an important role in peripheral nociception. However, whether TRPV1 and ANO1 are involved in estrogen-modulated trigeminal pain sensitivity is unclear. In this study, we examined 17β-estradiol (E2) modulation of nociception through behavioral and immunohistological experiments following application of capsaicin (Cap), a selective TRPV1 agonist, onto the ocular surface in ovariectomized rats treated with high- (HE) or low-dose E2 (LE) for 2 days...
September 30, 2016: Endocrinology
https://www.readbyqxmd.com/read/27676317/millimeter-wave-spectroscopy-x-ray-crystal-structure-and-quantum-chemical-studies-of-diketene-resolving-ambiguities-concerning-the-structure-of-the-ketene-dimer
#19
Vanessa L Orr, Brian J Esselman, P Matisha Dorman, Brent K Amberger, Ilia A Guzei, R Claude Woods, Robert J McMahon
The pure rotational spectrum of diketene has been studied in the millimeter-wave region from ∼240 to 360 GHz. For the ground vibrational state and five vibrationally excited satellites (ν24, 2ν24, 3ν24, 4ν24, and ν16), the observed spectrum allowed for the measurement, assignment, and least-squares fitting a total of more than 10 000 distinct rotational transitions. In each case, the transitions were fit to single-state, complete or near-complete sextic centrifugally distorted rotor models to near experimental error limits using Kisiel's ASFIT...
October 6, 2016: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/27640734/spectroscopy-and-photochemistry-of-triplet-1-3-dimethylpropynylidene-mec3me
#20
Stephanie N Knezz, Terese A Waltz, Benjamin C Haenni, Nicola J Burrmann, Robert J McMahon
Photolysis (λ > 472 nm) of 2-diazo-3-pentyne (11) affords triplet 1,3-dimethylpropynylidene (MeC3Me, (3)3), which was characterized spectroscopically in cryogenic matrices. The infrared, electronic absorption, and electron paramagnetic resonance spectra of MeC3Me ((3)3) are compared with those of the parent system (HC3H) to ascertain the effect of alkyl substituents on delocalized carbon chains of this type. Quantum chemical calculations (CCSD(T)/ANO1) predict an unsymmetrical equilibrium structure for triplet MeC3Me ((3)3), but they also reveal a very shallow potential energy surface...
September 28, 2016: Journal of the American Chemical Society
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