chloride channels

Summary

Summary: Cell membrane glycoproteins selective for chloride ions.

Top Publications

  1. pmc TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation
    Huanghe Yang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 94143, USA
    Cell 151:111-22. 2012
  2. pmc Expression cloning of TMEM16A as a calcium-activated chloride channel subunit
    Björn Christian Schroeder
    Department of Physiology, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
    Cell 134:1019-29. 2008
  3. ncbi TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
    Antonella Caputo
    Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy
    Science 322:590-4. 2008
  4. ncbi TMEM16A confers receptor-activated calcium-dependent chloride conductance
    Young Duk Yang
    Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    Nature 455:1210-5. 2008
  5. ncbi The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
    Hawon Cho
    Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
    Nat Neurosci 15:1015-21. 2012
  6. ncbi Anoctamins are a family of Ca2+-activated Cl- channels
    Yuemin Tian
    Institut fur Physiologie, Universitat Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany
    J Cell Sci 125:4991-8. 2012
  7. pmc Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?
    Charity Duran
    Emory University School of Medicine, Department of Cell Biology and Center for Neurodegenerative Disease, Atlanta, GA 30322, USA
    Acta Pharmacol Sin 32:685-92. 2011
  8. pmc Anoctamin 6 is an essential component of the outwardly rectifying chloride channel
    Joana Raquel Martins
    Institut fur Physiologie, Universitat Regensburg, D 93053 Regensburg, Germany
    Proc Natl Acad Sci U S A 108:18168-72. 2011
  9. pmc TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression
    Umamaheswar Duvvuri
    Department of Otolaryngology, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine and Magee Women s Research Institute, Pittsburgh, Pennsylvania 15213, USA
    Cancer Res 72:3270-81. 2012
  10. pmc Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topology
    Kuai Yu
    Department of Cell Biology, Emory University School of Medicine, 615 Michael St, Atlanta, GA 30322, USA
    Circ Res 110:990-9. 2012

Detail Information

Publications381 found, 100 shown here

  1. pmc TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation
    Huanghe Yang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 94143, USA
    Cell 151:111-22. 2012
    ..This study thus identifies a Ca(2+)-activated channel permeable to Ca(2+) and critical for Ca(2+)-dependent scramblase activity during blood coagulation. PAPERFLICK:..
  2. pmc Expression cloning of TMEM16A as a calcium-activated chloride channel subunit
    Björn Christian Schroeder
    Department of Physiology, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
    Cell 134:1019-29. 2008
    Calcium-activated chloride channels (CaCCs) are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction...
  3. ncbi TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
    Antonella Caputo
    Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy
    Science 322:590-4. 2008
    Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear...
  4. ncbi TMEM16A confers receptor-activated calcium-dependent chloride conductance
    Young Duk Yang
    Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    Nature 455:1210-5. 2008
    Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and ..
  5. ncbi The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
    Hawon Cho
    Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
    Nat Neurosci 15:1015-21. 2012
    ..These results indicate that ANO1 is a heat sensor that detects nociceptive thermal stimuli in sensory neurons and possibly mediates nociception...
  6. ncbi Anoctamins are a family of Ca2+-activated Cl- channels
    Yuemin Tian
    Institut fur Physiologie, Universitat Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany
    J Cell Sci 125:4991-8. 2012
    ..They may operate as Cl(-) channels located in the plasma membrane or in intracellular compartments. These results increase our understanding of the physiological significance of anoctamins and their role in disease...
  7. pmc Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?
    Charity Duran
    Emory University School of Medicine, Department of Cell Biology and Center for Neurodegenerative Disease, Atlanta, GA 30322, USA
    Acta Pharmacol Sin 32:685-92. 2011
    ..Here we review some of the recent developments in understanding the physiology and structure-function of the Tmem16 gene family...
  8. pmc Anoctamin 6 is an essential component of the outwardly rectifying chloride channel
    Joana Raquel Martins
    Institut fur Physiologie, Universitat Regensburg, D 93053 Regensburg, Germany
    Proc Natl Acad Sci U S A 108:18168-72. 2011
    Outwardly rectifying chloride channels (ORCC, ICOR) of intermediate single-channel conductance of around 50 pS, are ubiquitously expressed, but have remained a mystery since their description more than 25 y ago...
  9. pmc TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression
    Umamaheswar Duvvuri
    Department of Otolaryngology, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine and Magee Women s Research Institute, Pittsburgh, Pennsylvania 15213, USA
    Cancer Res 72:3270-81. 2012
    ..The development of small-molecule inhibitors against TMEM16A may be clinically relevant for treatment of human cancers, including SCCHN...
  10. pmc Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topology
    Kuai Yu
    Department of Cell Biology, Emory University School of Medicine, 615 Michael St, Atlanta, GA 30322, USA
    Circ Res 110:990-9. 2012
    ..Ca2+ -activated Cl channels were recently discovered to be encoded by members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca2+ remain enigmatic...
  11. pmc International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels
    Fen Huang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, Mission Bay Campus, San Francisco, CA 94158 2811, USA
    Pharmacol Rev 64:1-15. 2012
    Calcium-activated chloride channels (CaCCs) are widely expressed in various tissues and implicated in physiological processes such as sensory transduction, epithelial secretion, and smooth muscle contraction...
  12. ncbi Ion channels and cancer
    Karl Kunzelmann
    Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, Regensburg, D 93053, Germany
    J Membr Biol 205:159-73. 2005
    ..channels, like voltage-gated ether à go-go and Ca2+-dependent potassium channels as well as calcium and chloride channels, a cell cycle-dependent function has been demonstrated...
  13. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    ..Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA...
  14. pmc Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle
    Liang Feng
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA
    Science 330:635-41. 2010
    ..Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl(-)/H(+) exchange and a simple mechanistic connection between CLC channels and transporters...
  15. pmc A minimal isoform of the TMEM16A protein associated with chloride channel activity
    Loretta Ferrera
    Laboratorio di Genetica Molecolare, Largo Gerolamo Gaslini, Istituto Giannina Gaslini, 16147 Genova, Italy
    Biochim Biophys Acta 1808:2214-23. 2011
    ..However, the absence of alternative segments, which are present in more complex isoforms of TMEM16A, modifies the channel gating and ion transport ability...
  16. pmc The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels
    Boyi Liu
    Department of Pharmacology, Hebei Medical University, Shijiazhuang, China
    J Clin Invest 120:1240-52. 2010
    ..These results provide a framework for understanding spontaneous inflammatory pain and may suggest new drug targets for treatment of such pain...
  17. pmc Chloride channels: often enigmatic, rarely predictable
    Charity Duran
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Annu Rev Physiol 72:95-121. 2010
    ....
  18. pmc Regulation of TMEM16A chloride channel properties by alternative splicing
    Loretta Ferrera
    Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Largo G Gaslini 5, 16147 Genova
    J Biol Chem 284:33360-8. 2009
    ..Alternative splicing appears as an important mechanism to regulate the voltage and Ca(2+) dependence of the TMEM16A-dependent Cl(-) channels in a tissue-specific manner...
  19. ncbi Downregulation of TMEM16A calcium-activated chloride channel contributes to cerebrovascular remodeling during hypertension by promoting basilar smooth muscle cell proliferation
    Mi Wang
    Department of Pharmacology, Zhongshan School of Medicine, Sun Yat Sen University, 74 Zhongshan 2 Rd, Guangzhou, China
    Circulation 125:697-707. 2012
    ..The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity...
  20. pmc Calcium-activated chloride channels (CaCCs) regulate action potential and synaptic response in hippocampal neurons
    Wendy C Huang
    Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA
    Neuron 74:179-92. 2012
    ..Here, we report a mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs)...
  21. pmc ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification
    Aaron B Stephan
    Department of Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA
    Proc Natl Acad Sci U S A 106:11776-81. 2009
    ..Considering these findings together, we propose that ANO2 constitutes the olfactory calcium-activated chloride channel...
  22. ncbi Ca2+-activated Cl− currents are dispensable for olfaction
    Gwendolyn M Billig
    Leibniz Institut für Molekulare Pharmakologie FMP Max Delbrück Centrum für Molekulare Medizin MDC, Berlin, Germany
    Nat Neurosci 14:763-9. 2011
    ..In contrast with the current view, cyclic nucleotide-gated cation channels do not need a boost by Cl(-) channels to achieve near-physiological levels of olfaction...
  23. pmc ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity
    Lilia Leisle
    Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, Berlin, Germany
    EMBO J 30:2140-52. 2011
    ..Our work suggests that gating underlies the rectification of all endosomal/lysosomal CLCs and extends the concept of voltage gating beyond channels to ion exchangers...
  24. ncbi Calcium-activated chloride channels
    Criss Hartzell
    Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Physiol 67:719-58. 2005
    Calcium-activated chloride channels (CaCCs) play important roles in cellular physiology, including epithelial secretion of electrolytes and water, sensory transduction, regulation of neuronal and cardiac excitability, and regulation of ..
  25. pmc Drosophila bestrophin-1 chloride current is dually regulated by calcium and cell volume
    Li Ting Chien
    Department of Cell Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Gen Physiol 130:513-24. 2007
    ..We conclude that in addition to being regulated by intracellular Ca(2+), Drosophila bestrophins are also novel members of the volume-regulated anion channel (VRAC) family that are necessary for cell volume homeostasis...
  26. pmc Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 587:4887-904. 2009
    ..Loss of function of ANO1 did not inhibit the development of ICC networks that appeared structurally normal as indicated by Kit antibodies. These data demonstrate the fundamental role of ANO1 in the generation of slow waves in GI ICC...
  27. pmc TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells
    Wan Namkung
    Department of Medicine, University of California, San Francisco, California 94143, USA
    J Biol Chem 286:2365-74. 2011
    ..The small molecule inhibitors identified here permit pharmacological dissection of TMEM16A/CaCC function and are potential development candidates for drug therapy of hypertension, pain, diarrhea, and excessive mucus production...
  28. pmc TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A
    Joana Almaca
    Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, D 93053 Regensburg, Germany
    J Biol Chem 284:28571-8. 2009
    All vertebrate cells regulate their cell volume by activating chloride channels of unknown molecular identity, thereby activating regulatory volume decrease...
  29. ncbi Anoctamins
    Karl Kunzelmann
    Institut fur Physiologie, Universitat Regensburg, Universitätsstraße 31, Regensburg, Germany
    Pflugers Arch 462:195-208. 2011
    ..In order to understand how anoctamins produce Ca(2+)-activated Cl(-) currents, it will be necessary to obtain better insight into their molecular structure, interactions with partner proteins, and mode of activation...
  30. pmc Chloride channels as drug targets
    Alan S Verkman
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143 0521, USA
    Nat Rev Drug Discov 8:153-71. 2009
    b>Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets...
  31. ncbi TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals
    Heidi Stohr
    Institut fur Humangenetik, Universitat Regensburg, 93053 Regensburg, Germany
    J Neurosci 29:6809-18. 2009
    ..The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca(2+)-dependent chloride channel in the photoreceptor synapse...
  32. pmc Fluoride resistance and transport by riboswitch-controlled CLC antiporters
    Randy B Stockbridge
    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA
    Proc Natl Acad Sci U S A 109:15289-94. 2012
    ..Finally, F(-)/H(+) exchange occurs with 1:1 stoichiometry, in contrast to the usual value of 2:1...
  33. pmc Inhibition of cell proliferation by a selective inhibitor of the Ca(2+)-activated Cl(-) channel, Ano1
    Amelia Mazzone
    Enteric Neuroscience Program, Mayo Clinic, Rochester, MN 55905, USA
    Biochem Biophys Res Commun 427:248-53. 2012
    ..Indeed, a role for Ano1 in regulating proliferation of tumors and ICC has been recently suggested. Recently, a high-throughput screen identified a small molecule, T16A(inh)-A01 as a specific inhibitor of Ano1...
  34. ncbi Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation
    Stefanie Weinert
    Leibniz Institut fur Molekulare Pharmakologie FMP, 13125 Berlin, Germany
    Science 328:1401-3. 2010
    ..This conductance was even deleterious in Clcn7(+/unc) mice. Clcn7(-/-) and Clcn7(unc/unc) mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes...
  35. ncbi Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
    Ami Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, New York 14642, USA
    Mol Cell 10:35-44. 2002
    ..We propose that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM...
  36. pmc Glutamate-gated chloride channels
    Adrian J Wolstenholme
    Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
    J Biol Chem 287:40232-8. 2012
    Glutamate-gated chloride channels (GluCls) are found only in protostome invertebrate phyla but are closely related to mammalian glycine receptors...
  37. ncbi Molecular structure and physiological function of chloride channels
    Thomas J Jentsch
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Hamburg, Germany
    Physiol Rev 82:503-68. 2002
    ..Other gene families (CLIC or CLCA) were also reported to encode Cl- channels but are less well characterized. This review focuses on molecularly identified Cl- channels and their physiological roles...
  38. pmc Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis
    Gavin Charlesworth
    Department of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Am J Hum Genet 91:1041-50. 2012
    ..The locus DYT23 has been reserved as a synonym for this gene. The implication of an ion channel in the pathogenesis of dystonia provides insights into an alternative mechanism that opens fresh avenues for further research...
  39. pmc Expression and function of epithelial anoctamins
    Rainer Schreiber
    Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, D 93053 Regensburg, Germany
    J Biol Chem 285:7838-45. 2010
    ..We conclude that each tissue expresses a set of anoctamins that form cell- and tissue-specific Ca(2+)-dependent Cl(-) channels...
  40. pmc Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA
    Thurman M Wheeler
    Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Science 325:336-9. 2009
    ..These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs...
  41. ncbi TMEM16F is a component of a Ca2+-activated Cl- channel but not a volume-sensitive outwardly rectifying Cl- channel
    Takahiro Shimizu
    Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930 0194, Japan
    Am J Physiol Cell Physiol 304:C748-59. 2013
    ..These results demonstrate that human TMEM16F is an essential component of a Ca(2+)-activated Cl(-) channel with a Ca(2+) sensitivity that is distinct from that of TMEM16A/B and that it is not related to VSOR activity...
  42. pmc MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1
    Yoshihiro Kino
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    Nucleic Acids Res 37:6477-90. 2009
    ..Collectively, these results provide a mechanistic model for the regulation of Clcn1 splicing, and reveal novel regulatory properties of MBNL and CELF proteins...
  43. pmc Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels
    H Criss Hartzell
    Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Bldg, Atlanta, GA 30322, USA
    J Physiol 587:2127-39. 2009
    ..Some members of this family are up-regulated in a number of tumours and functional deficiency in others is linked to developmental defects...
  44. pmc Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract
    Pedro J Gomez-Pinilla
    Enteric Neuroscience Program, Miles and Shirley Fiterman Center for Digestive Diseases and Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Am J Physiol Gastrointest Liver Physiol 296:G1370-81. 2009
    ..Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells...
  45. ncbi Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
    Nicolas Charlet-B
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 10:45-53. 2002
    ..We propose that disruption of alternative splicing regulation causes a predominant pathological feature of DM1...
  46. pmc The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
    Robert B West
    Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
    Am J Pathol 165:107-13. 2004
    ..Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase...
  47. pmc TMEM16A/anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells
    Boris Manoury
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    J Physiol 588:2305-14. 2010
    Calcium-activated chloride channels (CaCCs) play important roles in several physiological processes...
  48. ncbi Excitatory actions of gaba during development: the nature of the nurture
    Yehezkel Ben-Ari
    Institut de Neurobiologie de la Méditerranée INMED, INSERM Unit 29, Parc Scientifique de Luminy, 13273 Marseille Cedex 09, France
    Nat Rev Neurosci 3:728-39. 2002
    ..As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks...
  49. ncbi The enigma of the CLIC proteins: Ion channels, redox proteins, enzymes, scaffolding proteins?
    Dene R Littler
    School of Physics, University of New South Wales, Sydney, NSW 2052, Australia
    FEBS Lett 584:2093-101. 2010
    ..The physiological role of CLICs appears to be maintenance of intracellular membranes, which is associated with tubulogenesis but may involve other substructures...
  50. ncbi Involvement of the intracellular ion channel CLIC1 in microglia-mediated beta-amyloid-induced neurotoxicity
    Gaia Novarino
    Dipartimenti di Biologia Cellulare e dello Sviluppo, Universita La Sapienza, 00185 Rome, Italy
    J Neurosci 24:5322-30. 2004
    ..These results provide a direct link between Abeta-induced microglial activation and CLIC1 functional expression...
  51. pmc ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins
    Charity Duran
    Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322 3030, USA
    Am J Physiol Cell Physiol 302:C482-93. 2012
    ..Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease...
  52. ncbi Metamorphic response of the CLIC1 chloride intracellular ion channel protein upon membrane interaction
    Sophia C Goodchild
    Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia
    Biochemistry 49:5278-89. 2010
    ..Consistent with previous findings, the N-terminal domain of CLIC1 is likely to insert into the lipid bilayer, while the C-domain remains in solution on the extravesicular side of the membrane...
  53. pmc Anoctamins and gastrointestinal smooth muscle excitability
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Exp Physiol 97:200-6. 2012
    ..Anoctamin 1 is a prominent conductance in ICC, and these channels appear to be involved in pacemaker activity and in responses to enteric excitatory neurotransmitters...
  54. pmc Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop
    Qinghuan Xiao
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 108:8891-6. 2011
    ..This mechanism provides a unified explanation of CaCC channel gating by voltage and ligand that has long been enigmatic...
  55. ncbi The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels
    Yoshihisa Ozoe
    Department of Life Science and Biotechnology, Shimane University, Matsue, Shimane 690 8504, Japan
    Biochem Biophys Res Commun 391:744-9. 2010
    ..we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively...
  56. pmc Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons
    Michele Dibattista
    Neurobiology Sector and Italian Institute of Technology Unit, Scuola Internazionale Superiore di Studi Avanzati SISSA, 34136 Trieste, Italy
    J Gen Physiol 140:3-15. 2012
    ..Furthermore, we showed by immunohistochemistry that the calcium-activated chloride channels TMEM16A/anoctamin1 and TMEM16B/anoctamin2 are present in the apical layer of the vomeronasal epithelium, ..
  57. ncbi TMEM16B induces chloride currents activated by calcium in mammalian cells
    Simone Pifferi
    International School for Advanced Studies, Scuola Internazionale Superiore di Studi Avanzati SISSA, Via Beirut 2, 34014, Trieste, Italy
    Pflugers Arch 458:1023-38. 2009
    ..Our results demonstrate that mTMEM16B functions as a Ca(2+)-activated Cl(-) channel when expressed in HEK 293T cells...
  58. ncbi TMEM16A protein: a new identity for Ca(2+)-dependent Cl⁻ channels
    Loretta Ferrera
    Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Genova, Italy
    Physiology (Bethesda) 25:357-63. 2010
    ..The recent identification of TMEM16A protein as an important component of CaCCs should allow a better understanding of their physiological role, structure-function relationship, and regulatory mechanisms...
  59. ncbi DOG1 antibody is a highly sensitive and specific marker for gastrointestinal stromal tumors in cytology cell blocks
    Dick G Hwang
    Dept of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Clin Pathol 135:448-53. 2011
    ..KIT was positive in 46 (88%) of the GIST cases, with sensitivity dependent on the FNA method. Both markers were highly specific: KIT was negative in all 44 non-GIST cases, whereas DOG1 showed weak positivity in only 1 leiomyosarcoma...
  60. ncbi Expression and function of epithelial anoctamins
    Karl Kunzelmann
    Universitat Regensburg, Institut fur Physiologie, Universitätsstraße 31, Regensburg, Germany
    Exp Physiol 97:184-92. 2012
    ..Most available data on anoctamins were obtained from mouse tissues and from cultured cells, which may not be representative of native human tissues...
  61. ncbi The spectrum of ocular phenotypes caused by mutations in the BEST1 gene
    Camiel J F Boon
    Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Prog Retin Eye Res 28:187-205. 2009
    ..The genotype-phenotype correlations that are observed in association with BEST1 mutations are discussed. In addition, in vitro studies and animal models that clarify the pathophysiological mechanisms are reviewed...
  62. pmc Ionic currents mediated by a prokaryotic homologue of CLC Cl- channels
    Alessio Accardi
    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA
    J Gen Physiol 123:109-19. 2004
    ..These effects correlate well with known characteristics of eukaryotic CLC channels. The E148A mutant displays nearly ideal Cl- selectivity...
  63. pmc Studies on expression and function of the TMEM16A calcium-activated chloride channel
    Fen Huang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 106:21413-8. 2009
    Calcium-activated chloride channels (CaCC) with similar hallmark features are present in many cell types and mediate important physiological functions including epithelial secretion, sensory signal transduction, and smooth muscle ..
  64. pmc Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa
    Alice E Davidson
    Genetic Medicine, The University of Manchester, Manchester Academic Heath Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
    Am J Hum Genet 85:581-92. 2009
    ..L140V and p.D228N) caused mislocalization of bestrophin-1 from the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are increasingly recognized as an important cause of inherited retinal dystrophy...
  65. pmc Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways
    Jason R Rock
    Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27708, USA
    J Biol Chem 284:14875-80. 2009
    ..Our data suggest that TMEM16A CaCC-mediated Cl(-) secretion appears to be necessary for normal airway surface liquid homeostasis...
  66. ncbi A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors
    Inigo Espinosa
    Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA
    Am J Surg Pathol 32:210-8. 2008
    ..5%) synovial sarcomas among the 935 soft tissue tumors examined showed positive immunostaining for DOG1.1. In addition, DOG1.1 immunoreactivity was seen in fewer cases of carcinoma, melanoma, and seminoma as compared with KIT...
  67. pmc Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium
    A D Marmorstein
    Department of Ophthalmic Research, Cole Eye Institute, and Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195, USA
    Proc Natl Acad Sci U S A 97:12758-63. 2000
    ..The basolateral plasma membrane localization of bestrophin suggests the possibility that bestrophin plays a role in generating the altered electrooculogram of individuals with Best disease...
  68. ncbi Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death
    Y Okada
    Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444 8585, Japan
    J Membr Biol 209:21-9. 2006
    ..The apoptosis-inducing VSOR Cl(-) channel is distinct from ClC-3 and its molecular identity remains to be determined...
  69. ncbi Calcium-activated chloride channels: (un)known, (un)loved?
    Jan Eggermont
    Laboratory of Physiology, Katholieke Universiteit Leuven, Campus Gasthuisberg, B 3000 Leuven, Belgium
    Proc Am Thorac Soc 1:22-7. 2004
    Calcium-activated chloride channels (CaCCs) participate in many different physiologic processes such as transepithelial transport, excitability of neurons and muscle cells, and oocyte fertilization...
  70. pmc Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
    Thurman M Wheeler
    Department of Neurology, University of Rochester, Rochester, New York 14618, USA
    J Clin Invest 117:3952-7. 2007
    ....
  71. ncbi Noninvasive measurement of chloride concentration in rat olfactory receptor cells with use of a fluorescent dye
    H Kaneko
    Department of Applied Physics and Chemistry, Division of Bio-Informatics, The University of Electro-Communications, Chofu, Tokyo 182 - 8585, Japan
    Am J Physiol Cell Physiol 280:C1387-93. 2001
    ..They provide a starting point for the decrease in ciliary [Cl(-)] predicted to occur during transduction...
  72. pmc Distinct expression/function of potassium and chloride channels contributes to the diverse volume regulation in cortical astrocytes of GFAP/EGFP mice
    Jana Benesova
    Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    PLoS ONE 7:e29725. 2012
    ..Thus, we propose that the diverse volume changes displayed by cortical astrocytes during OGD mainly result from their distinct expression patterns of ClC2 and K(2P) channels...
  73. ncbi Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp-2 cells via reactive oxygen species production
    Jae Sung Kim
    Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
    Proteomics 10:2589-604. 2010
    ....
  74. ncbi Anoctamin 2/TMEM16B: a calcium-activated chloride channel in olfactory transduction
    Simone Pifferi
    SISSA, International School for Advanced Studies, and Italian Institute of Technology, SISSA Unit, via Bonomea 265, 34136 Trieste, Italy
    Exp Physiol 97:193-9. 2012
    ..Finally, we discuss the involvement of Ca(2+)-activated Cl(-) channels in the transduction process of vomeronasal sensory neurons and the physiological role of these channels in olfaction...
  75. pmc Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal
    Mei Hong Zhu
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:4565-82. 2011
    ..These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation...
  76. ncbi Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1
    Sarah N R Pressey
    Pediatric Storage Disorders Laboratory, Department of Neuroscience, Centre for the Cellular Basis of Behavior, Institute of Psychiatry, King s College London, UK
    J Neuropathol Exp Neurol 69:1228-46. 2010
    ....
  77. pmc Sorting motifs of the endosomal/lysosomal CLC chloride transporters
    Tobias Stauber
    Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Berlin D 13125, Germany
    J Biol Chem 285:34537-48. 2010
    The CLC protein family contains plasma membrane chloride channels and the intracellular chloride-proton exchangers ClC-3-7...
  78. ncbi Astrocytes from mouse brain slices express ClC-2-mediated Cl- currents regulated during development and after injury
    Judit K Makara
    Department of Physiology and Laboratory of Cellular and Molecular Physiology, Semmelweis University Medical School, Budapest, Hungary
    Mol Cell Neurosci 23:521-30. 2003
    b>Chloride channels are important for astrocytic volume regulation and K+ buffering...
  79. ncbi Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma
    Ying Hwa Chang
    Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    J Proteome Res 8:5465-74. 2009
    ..Our results indicate that the analytical platform could provide a feasible strategy to profile tumor cell secretome for identifying cancer biomarkers, and CLIC1 may be a novel plasma tumor marker for NPC...
  80. pmc Rescue of volume-regulated anion current by bestrophin mutants with altered charge selectivity
    Li Ting Chien
    Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Gen Physiol 132:537-46. 2008
    ..VRACs were identical in wild-type and best1(-/-)/best2(-/-) mice, showing that bestrophins are unlikely to be the classical VRAC in mammalian cells...
  81. ncbi Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel
    Ricardo de la Fuente
    1246 Health Sciences East Tower, Box 0521, University of California, San Francisco CA 94143 0521, USA
    Mol Pharmacol 73:758-68. 2008
    Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available...
  82. pmc Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons
    Sangseong Kim
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Nat Commun 2:365. 2011
    ..Recently, calcium-activated chloride channels have been shown to contribute to VNO activation...
  83. ncbi A flow-activated chloride-selective membrane current in vascular endothelial cells
    A I Barakat
    Department of Mechanical and Aeronautical Engineering, University of California, Davis, CA 95616, USA
    Circ Res 85:820-8. 1999
    ..Membrane potential sensitivity to flow was unchanged by flow preconditioning that elongated and aligned the cells...
  84. pmc Functional and clinical data of Best vitelliform macular dystrophy patients with mutations in the BEST1 gene
    Giuseppe Querques
    Department of Ophthalmology, Hopital Intercommunal de Creteil, University Paris XII, Paris, France
    Mol Vis 15:2960-72. 2009
    ..To analyze functional and clinical data of Best vitelliform macular dystrophy (VMD) patients with mutations in the BEST1 gene...
  85. pmc Principles of activation and permeation in an anion-selective Cys-loop receptor
    Ryan E Hibbs
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 474:54-60. 2011
    ..GluCl provides a framework for understanding mechanisms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors...
  86. ncbi Tmem16b is specifically expressed in the cilia of olfactory sensory neurons
    Sebastian Rasche
    Neuroscience Research Center, Charite, Universitatsmedizin Berlin, 10117 Berlin, Germany
    Chem Senses 35:239-45. 2010
    Calcium-activated chloride channels (CaCCs) are involved in many physiological processes, including sensory signal transduction, but only little is known to date about their structure and function...
  87. ncbi A point mutation in a Drosophila GABA receptor confers insecticide resistance
    R H ffrench-Constant
    Department of Entomology, 237 Russell Laboratories, University of Wisconsin, Madison 53706
    Nature 363:449-51. 1993
    ....
  88. pmc Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel
    Yasunobu Okada
    Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji cho, Okazaki 444 8585, Japan
    J Physiol 587:2141-9. 2009
    ..Molecular identification of VSOR is required to address the question of how cells sense volume expansion and activate VSOR...
  89. pmc CLC channels and transporters: proteins with borderline personalities
    Alessio Accardi
    Department of Molecular Physiology and Biophysics, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Biochim Biophys Acta 1798:1457-64. 2010
    ..This review focuses on the recent mechanistic insights on the how the structural similarities between CLC channels and transporters translate in unexpected mechanistic analogies between these two sub-classes...
  90. ncbi Modulation of GABAergic transmission by activity via postsynaptic Ca2+-dependent regulation of KCC2 function
    Hubert Fiumelli
    Division of Neurobiology, Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California 94720, USA
    Neuron 48:773-86. 2005
    ..Thus, repetitive postsynaptic spiking reduces the inhibitory action of GABA through a Ca2+-dependent downregulation of KCC2 function...
  91. ncbi Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies
    H Criss Hartzell
    Department of Cell Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Physiol Rev 88:639-72. 2008
    ..Bestrophins are also regulated by cell volume and may be a member of the volume-regulated anion channel family...
  92. ncbi Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice
    C A Gurnett
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA
    J Biol Chem 270:9035-8. 1995
    ..Immunohistochemistry of skeletal muscle from ADR and other mouse models of human muscle disease demonstrate that the absence of ClC-1 chloride channel is a defect specific to ADR mice...
  93. ncbi Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis
    Gaia Novarino
    Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, 13125 Berlin, Germany
    Science 328:1398-401. 2010
    ..However, their proximal tubular endocytosis was also impaired. Thus, endosomal chloride concentration, which is raised by ClC-5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis...
  94. ncbi Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists
    L V Galietta
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    Am J Physiol Cell Physiol 281:C1734-42. 2001
    ..The fluorescence assay and cell lines should facilitate the screening of novel CFTR activators and the characterization of alternative Cl(-) channels and transporters...
  95. pmc Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin
    N S Kane
    Merck Research Laboratories, Merck and Co, Inc, PO Box 2000, R80Y 250, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 97:13949-54. 2000
    ....
  96. ncbi Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration
    F Kramer
    Institut fur Humangenetik, Universitat Wurzburg, Germany
    Eur J Hum Genet 8:286-92. 2000
    ..There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD...
  97. pmc Functional properties of murine bestrophin 1 channel
    Kate E O'Driscoll
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, 1664 N Virginia Street, Reno, NV 89557, USA
    Biochem Biophys Res Commun 384:476-81. 2009
    ..Our study provides the first characterization of the biophysical properties of mBest1 and a framework for the elucidation of the physiological role of bestrophins...
  98. pmc Ligand-gated chloride channels are receptors for biogenic amines in C. elegans
    Niels Ringstad
    Howard Hughes Medical Institute, Department of Biology, and McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA
    Science 325:96-100. 2009
    ..We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-..
  99. ncbi Contribution of chloride channels to volume regulation of cortical astrocytes
    Kimberly A Parkerson
    Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Am J Physiol Cell Physiol 284:C1460-7. 2003
    ..These data suggest that Cl(-) flux through ion channels rather than transporters is essential for volume regulation of cultured astrocytes in response to hypotonic challenge...
  100. pmc Ano1 as a regulator of proliferation
    Jennifer E Stanich
    Enteric Neuroscience Program, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Physiol Gastrointest Liver Physiol 301:G1044-51. 2011
    ..These data led us to conclude that Ano1 regulates proliferation at the G(1)/S transition of the cell cycle and may play a role in tumorigenesis...
  101. pmc Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels
    Lukmanee Tradtrantip
    Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    Mol Pharmacol 77:69-78. 2010
    ..5 microM. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl(-) channels may account for its intestinal antisecretory activity...

Research Grants73

  1. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2006
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  2. Iowa Phase II Clinical Trials of Novel Therapies for Lung Diseases (U01
    Lakshmi Durairaj; Fiscal Year: 2012
    ..Disruption of the cystic fibrosis transmembrane conductance regulator chloride channels due to genetic mutations in subjects with CF results in altered fluid and electrolyte transport across the ..
  3. High affinity capturing agents for strychnine
    Kit S Lam; Fiscal Year: 2011
    ..The binding affinity as well as interaction mode between strychnine and the capturing agents will be fully characterized. ..
  4. Development of Bioactive Chemical Probes for Calcium-activated Chloride Channel
    Min Li; Fiscal Year: 2012
    ..Therefore, specific modulation compounds are useful to aid therapeutic development. ..
  5. ClC-3 Chloride Ion Channels in Vascular Smooth Muscle
    Fred Lamb; Fiscal Year: 2009
    ..abstract_text> ..
  6. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Chloride channels and transporters of the CLC family play crucial roles in a myriad of physiological processes including regulation of electrical excitability of nerve and muscle cells, modulation of ..
  7. CFTR Biogenesis and Function in Epithelia
    Zsuzsa Bebok; Fiscal Year: 2012
    ..Understanding these processes are important in understanding the cellular basis for a number of lung pathologies including cystic fibrosis and chronic obstructive pulmonary disease (COPD). ..
  8. Transcriptional Networks Regulating Luminal Environment in the Epididymis
    Ann Harris; Fiscal Year: 2013
    ..Through modulation of this environment we may also be able to inhibit normal sperm maturation and thereby develop novel methods of birth control. ..
  9. Pathological Evaluation of a Cystic Fibrosis Ferret Model
    John F Engelhardt; Fiscal Year: 2010
    ..This model shows classic signs of human CF disease and may be a valuable resource for the CF research community following completion of the proposed project. ..
  10. Cholinergic Receptors as Targets for Accelerated Anthelmintic Discovery
    MICHAEL JOHN KIMBER; Fiscal Year: 2013
    ..forming the substrate of this proposal are G protein-coupled acetylcholine receptors and acetylcholine-gated chloride channels in the parasitic nematode B. malayi and the parasitic flatworm Schistosoma mansoni...
  11. Early Pathogenesis of Cystic Fibrosis Related Diabetes
    Andrew W Norris; Fiscal Year: 2013
    ..Although the application focuses on early disease pathophysiology, it also has great potential for identifying blood biomarkers for early diagnosis of patients at risk for CFRD. ..
  12. VOLUME REGULATION IN NORMAL AND CATARACTOUS LENSES
    Richard T Mathias; Fiscal Year: 2013
    ..and extracellular fluxes are linked by fiber cell membranes, which express nonselective cation channels, chloride channels and the water channel AQP0...
  13. Analysis of PTH and Dopamine Receptor Signaling in Proximal Tubules
    Eleanor D Lederer; Fiscal Year: 2013
    ..Thus understanding how the kidney regulates phosphate homeostasis has significant relevance to the health of Veterans of all ages. ..
  14. DOSAGE COMPENSATION OF THE ACTIVE X CHROMOSOME IN MAMMALS
    Christine M Disteche; Fiscal Year: 2010
    ..Maintenance of the balance of gene expression is critical for normal development, as can be seen from the presence of multiple congenital abnormalities in individuals with chromosomal imbalance due to autosomal monosomy. ..
  15. TGF-BETA, CHLORIDE CHANNELS AND MIGRATION OF EOSINOPHILS
    Devendra K Agrawal; Fiscal Year: 2012
    ..The information obtained from this study should provide an opportunity to formulate superior therapeutic approaches in chronic asthma. ..
  16. Molecular-Genetic Dissection of Basal Forebrain Circuitry Regulating Arousal
    PATRICK MICHAEL FULLER; Fiscal Year: 2013
    ....
  17. Cholesterol and Sphingolipid Perturbation of Membrane Traffic in Human Disease
    Andrew H Limper; Fiscal Year: 2011
    ..The following studies will examine the role of these lipids in exacerbating the symptoms of Cystic fibrosis and will be used in developing new therapeutic approaches for this disease. ..
  18. MOLECULAR MECHANISMS FOR EXTRACELLULAR PH CONTROL DURING AMELOGENESIS
    MICHAEL LANSDELL PAINE; Fiscal Year: 2013
    ..This study will raise awareness of dental disease in a large but select group of seriously ill patients where their disease is closely linked to pH regulation. ..
  19. Role of Ion Channel in Mononuclear Phagocyte Activation
    Deborah J Nelson; Fiscal Year: 2012
    ..CFTR and ClC-3 chloride channels are the most reasonable channels with which to begin our studies given our preliminary data on CFTR in ..
  20. Cisplatin Resistance mediated by copper export pathways
    Stephen B Howell; Fiscal Year: 2013
    ....
  21. Role of Calcium-Activated Chloride Channels in Airway Disease Phenotypes
    ANAND CHAMPAK PATEL; Fiscal Year: 2011
    ..These proposed experiments should serve to define CLCA function in experimental asthma and thereby provide for new therapeutic targets in humans with airway disease. ..
  22. CHLORIDE CHANNELS IN LUNG DEVELOPMENT
    Pamela L Zeitlin; Fiscal Year: 2012
    ..We have proposed that alternative chloride channels can be exploited to bypass the CFTR defect...
  23. Toxic metals and ion channels in cigarette-smoke induced COPD
    ESTELLE A CORMET BOYAKA; Fiscal Year: 2010
    ..We found that cadmium can suppress the Cystic Fibrosis Transmembrane conductance Regulator, a chloride channel that when dysfunctional leads to cystic fibrosis. (End of Abstract) ..
  24. Molecular, Genetic &Physiological Studies of Calcium-activated Chloride Channels
    Lily Y Jan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Calcium-activated chloride channels (CaCCs) serve important physiological functions including modulation of signal processing of a variety of central and peripheral neurons...
  25. CFTR inhibitors for therapy of polycystic kidney disease
    Alan S Verkman; Fiscal Year: 2010
    ..This new form of therapy might ultimately prolong kidney function in polycystic kidney disease. ..
  26. Xenon MRI assessment of response to cystic fibrosis therapies
    IULIAN CONSTANTIN RUSET; Fiscal Year: 2012
    ..The proposed study is a vital step toward determining whether HXe MRI could be a useful outcome measure in CF, something that could have tremendous clinical impact in this patient population. ..
  27. Development of a Humanized Pig Model of Cystic Fibrosis
    Christopher Rogers; Fiscal Year: 2010
    ..Thus, this work will accelerate the discovery of novel therapies for this lethal disease. ..
  28. A novel biotherapeutic for triple-negative breast cancer.
    Randolph C Elble; Fiscal Year: 2010
    ..We determine how it causes tumor cell death. We determine the structural feature responsible and its target on the tumor cell. ..
  29. Tissue-specific regulation of a gene essential for airway epithelial function
    Ann Harris; Fiscal Year: 2012
    ..Translational opportunities that may arise from this work include modulating CFTR expression in vivo and the construction of efficient, tissue-specific gene therapy vectors. ..
  30. Phase II Therapeutic Trial of Mexiletine
    Richard J Barohn; Fiscal Year: 2010
    ..Most cases of NDM are related to mutations in voltage-dependent sodium or chloride channels. Mexiletine is a class 1B antiarrhythmic medication that has high affinity for muscle sodium channels...
  31. Therapeutic correction of deltaF508-CFTR cystic fibrosis by a novel PDZ12 drug.
    Alvin Bach; Fiscal Year: 2013
    ..PDZ1-2 is a well-validated therapeutic target in CF that influences both the CF chloride channels trafficking and anchoring at the cell membrane, and its activation...
  32. Regulation of ClC-3 in Human Malignant Glioma
    Vishnu Anand Cuddapah; Fiscal Year: 2012
    ..Therefore understanding the unique features of glioblastoma biology will lead to the identification of novel targets for the development of therapeutic agents leading to better clinical outcomes. ..
  33. rAAV-directed gene therapy to the lung in cystic fibrosis ferret models
    John F Engelhardt; Fiscal Year: 2013
    ..This proposal will significantly enhance the field's ability to effectively develop therapeutic strategies for treatment of the CF lung, not only using rAAV vectors, but also other pharmacologic and gene-based therapies. ..
  34. Generation and validation of a comprehensive human disease mutant ORF resource
    Luke J Whitesell; Fiscal Year: 2010
    ..The never before achievable insights will dramatically improve the translation of current genetic knowledge to actual improvements in treatment and outcome for patients. ..
  35. Role of Collecting Duct Chloride Transporters in Volume Regulation
    Manoocher Soleimani; Fiscal Year: 2013
    ..They will further provide novel therapeutic insights in patients with diuretic resistance, salt sensitive hypertension and altered acid base homeostasis. ..
  36. OPTIMIZE - CCC - Lead Application
    Bonnie W Ramsey; Fiscal Year: 2013
    ..Previously unstudied characteristics of the respiratory microbiome predictive of poor microbiologic and/or clinical response will be identified. This CCC lead application is submitted with a DCC application. ..
  37. Radiovirotherapy for Multiple Myeloma
    Stephen J Russell; Fiscal Year: 2012
    ..The studies to be pursued in this grant combine the promising novel approach of oncolytic virotherapy with the use of radioactive iodine for the treatment of this disease. ..
  38. Can drug targets from parasitic nematodes be usefully expressed in C. elegans?
    ADRIAN JOHN WOLSTENHOLME; Fiscal Year: 2013
    ....
  39. Cytoskeletal linking proteins in renal epithelial cell function
    R Brian Doctor; Fiscal Year: 2012
    ....
  40. OPTIMIZE - DCC
    Nicole Mayer Hamblett; Fiscal Year: 2013
    ..Previously unstudied characteristics of the respiratory microbiome predictive of poor microbiologic and/or clinical response will be identified. This CCC lead application is submitted with a DCC application. ..
  41. The Peripheral and Central Neuronal Circuits that Underlie Itch
    Hyosang Lee; Fiscal Year: 2012
    ....
  42. Peptide Inhibitors Probe Structure and Function in Chloride Channels
    Nael A McCarty; Fiscal Year: 2013
    ABSTRACT Chloride channels play crucial roles in many aspects of cell physiology. The genes encoding these channels are the loci for several human diseases relevant to the NIDDK...
  43. Chloride Channel Involvement in Diabetes
    Deborah J Nelson; Fiscal Year: 2012
    ..A better understanding of how chloride channel activity regulated and its relationship with insulin-secretion deficiency may lead to the development of new therapies that ameliorate the course of type 2 diabetes. ..
  44. Molecular genetic dissection of central amygdala microcircuitry underlying fear a
    David J Anderson; Fiscal Year: 2013
    ....
  45. Molecular Physiology of CLC Chloride Channels
    Tsung Yu Chen; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: This application will study CLC channels, which are chloride channels critical for chloride ion transports across cell membranes...
  46. Microbiome acquistion and the progression of inflammation and airway disease in i
    Barbara I Kazmierczak; Fiscal Year: 2013
    ..End of Abstrct) ..
  47. Target Validation and Assay Development for Anti-Mucus Therapy
    Michael J Holtzman; Fiscal Year: 2012
    ..This proposal aims directly at this issue by validating a new mechanism to explain overproduction of ainA^ay mucus during disease and by taking the next steps to identify the means to monitor and treat this abnormality. ..
  48. STRUCTURE AND FUNCTION OF LENS CHANNELS
    JAMES EWBANK HALL; Fiscal Year: 2013
    ..Lens cells have glucose transporters, chloride channels, sodium and potassium channels, gap junctions, and many other standard transport proteins in common with the ..
  49. Development of inhibitors of the calcium-activated chloride channel TMEM16a
    Marc O Anderson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Chloride channels have important roles in normal human physiology, and their dysfunction is involved in a number of diseases...
  50. Bestrophin Channel Function in Heart
    FIONA CATHERINE BRITTON; Fiscal Year: 2012
    ..are a novel family of proteins that have recently been described to function as calcium-activated chloride channels. The overall goal of our research is to understand the mechanisms by which Bestrophin ion channels mediate ..
  51. The Role of PLEKHM1 in Osteoclast Function
    Haibo Zhao; Fiscal Year: 2010
    ..We plan to determine how this new protein regulates the osteoclast, raising the possibility that we will be able to develop a new drug that prevents bone loss. ..
  52. Mechanisms and Binding-Sites in Adenylate Kinase-Dependent CFTR Gating
    CHRISTOPH OSKAR RANDAK; Fiscal Year: 2013
    ..Because CFTR is an ABC transporter, this knowledge may also impact treatments of other ABC transporter-related diseases. (End of Abstract) ..
  53. Correction of defective deltaF508-CFTR processing in cystic fibrosis
    Gergely L Lukacs; Fiscal Year: 2013
    ..Aim 3. Will determine the translational potential of LSDS-based combination ?F508-CFTR corrector therapy by using innovate surrogate human cellular and animal models of CF. ..
  54. Assay for GI Drug Discovery
    LID WONG; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Chloride channels and proton transporters are the two predominant drug discovery gastrointestinal (GI) target sites for the ..
  55. Regional Quantification of Lung Function in Cystic Fibrosis using Xe129 MRI
    Jaime Mata; Fiscal Year: 2013
    ..All subjects under this aim will also receive full pulmonary function tests (PFTs) to evaluate the degree of disease severity and to correlate with the results from 3D SB-CSI. ..
  56. MOLECULAR GENETICS OF CYSTIC FIBROSIS
    Garry R Cutting; Fiscal Year: 2012
    ..cAMP-dependent pathways, 4) generation of endogenous CI- currents and 5) regulation of separate sodium and chloride channels (and possibly other channels and transporters)...
  57. Molecular Physiology and Pharmacology of CFTR
    SILVIA BOMPADRE; Fiscal Year: 2009
    ..Results from this work will provide invaluable information to help the understanding of one of the most common disease-associated mutations in patients with CF as well as shed light on the mechanisms that enhance CFTR activity. ..
  58. Cell Biology of CFTR in Polarized Epithelia
    James F Collawn; Fiscal Year: 2013
    ..Our goal is to understand how the molecular machinery recognizes aberrant proteins at the plasma membrane. The results of this study are relevant in the analysis of other protein folding diseases. ..
  59. Epigenomic Modulation of Cystic Fibrosis
    WILLIAM EDWARD BALCH; Fiscal Year: 2013
    ....
  60. The CLC-3 chloride channels in the heart
    DAYUE DARREL DUAN; Fiscal Year: 2013
    ....
  61. Role of ion channels in the development of COPD
    ESTELLE A CORMET-BOYAKA; Fiscal Year: 2013
    ..This proposal will also identify the role of CFTR in lung responses to cigarette smoking. These studies will identify new markers that could be targeted for therapy. ..
  62. Regulation of Calcium Activated Chloride Channels
    H Criss Hartzell; Fiscal Year: 2013
    ..This application will focus on an exciting new family of chloride channels that was just discovered, the anoctamins (also called TMEM16)...
  63. TMEM16A Channel Stoichiometry and Subunit Interaction
    Jason Tien; Fiscal Year: 2013
    ....
  64. Regulation of Epithelial Sodium Channel by CFTR chloride channel
    Bakhrom Berdiev; Fiscal Year: 2009
    ....
  65. GABAERGIC INSECTICIDE TOXICOLOGY
    JOHN CASIDA; Fiscal Year: 2002
    ....
  66. REGULATION OF THE GABA RECEPTOR-CHLORIDE ION CHANNEL
    ROCHELLE SCHWARTZ BLOOM; Fiscal Year: 1991
    ..This research should reveal the importance of these mechanisms in the actions of convulsant and anticonvulsant drugs and in the physiology of seizure activity itself...
  67. FUNCTIONAL ANALYSIS OF NOVEL GABA RECEPTOR IN DROSOPHILA
    Richard ffrench Constant; Fiscal Year: 1999
    ..He has functionally expressed in Xenopus oocytes GABA-gated chloride channels composed of homomultimers of Rdl and rescued the susceptible phenotype by P element mediated germline ..
  68. Daily genistein injections stimulate intestinal secretion: How?
    Layla Al Nakkash; Fiscal Year: 2007
    ..Furthermore, we aim to identify the suitability of genistein as a potential therapeutic for the most common lethal genetic disease in Caucasians, cystic fibrosis (CF). [unreadable] [unreadable] [unreadable]..
  69. Role of Myosin VI in CFTR Endocytosis in the Intestine
    Nadia Ameen; Fiscal Year: 2007
    ..anion secretion in the intestine. The additional funds provided by this award will enable the PI to expand investigations and develop collaborations as she pursues these revised specific aims. [unreadable] [unreadable]..
  70. ACTIVATION OF CFTR MUTANTS IN VIVO FOR CF THERAPY
    MITCHELL DRUMM; Fiscal Year: 1999
    ..If beta-adrenergic agonists and class-specific phospho-diesterase inhibitors can significantly increase chloride transport, it is important to carry out studies on mechanism to determine if the process can be further improved. ..
  71. Rescue of CFTR-deltaF508 misfolding by pharmacological and genetic suppressors
    RYAN TYLER; Fiscal Year: 2009
    ..The broad objective of our studies is to uncover leads that could translate into new treatments for cystic fibrosis. ..
  72. CHLORIDE CHANNELS IN A MODEL EPITHELIUM--GALLBLADDER
    ARTHUR FINN; Fiscal Year: 1991
    ..We plan to characterize these apical chloride channels in physiological terms, to develop a monoclonal antibody to them, and to characterize the specific protein(s)..
  73. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2006
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...