calcium channels

Summary

Summary: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.

Top Publications

  1. ncbi The capsaicin receptor: a heat-activated ion channel in the pain pathway
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143 0450, USA
    Nature 389:816-24. 1997
  2. ncbi Calcium signalling: dynamics, homeostasis and remodelling
    Michael J Berridge
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    Nat Rev Mol Cell Biol 4:517-29. 2003
  3. ncbi The versatility and universality of calcium signalling
    M J Berridge
    The Babraham Institute, Laboratory of Molecular Signalling, Babraham Hall, Babraham, Cambridge, CB2 4AT, UK
    Nat Rev Mol Cell Biol 1:11-21. 2000
  4. pmc STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx
    Jen Liou
    Department of Molecular Pharmacology, Stanford University Medical School, California 94305, USA
    Curr Biol 15:1235-41. 2005
  5. ncbi A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function
    Stefan Feske
    The CBR Institute for Biomedical Research, and the Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 441:179-85. 2006
  6. pmc Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
    Joshua M Baughman
    Department of Systems Biology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nature 476:341-5. 2011
  7. pmc STIM1, an essential and conserved component of store-operated Ca2+ channel function
    Jack Roos
    Torrey Pines Therapeutics, Inc, La Jolla, CA 92037, USA
    J Cell Biol 169:435-45. 2005
  8. ncbi Store-operated calcium channels
    Anant B Parekh
    Department of Physiology, University of Oxford, United Kingdom
    Physiol Rev 85:757-810. 2005
  9. pmc A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
    Diego De Stefani
    Department of Biomedical Science, University of Padua, 35121 Padua, Italy
    Nature 476:336-40. 2011
  10. ncbi Orai1 is an essential pore subunit of the CRAC channel
    Murali Prakriya
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Nature 443:230-3. 2006

Detail Information

Publications298 found, 100 shown here

  1. ncbi The capsaicin receptor: a heat-activated ion channel in the pain pathway
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143 0450, USA
    Nature 389:816-24. 1997
    ..The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo...
  2. ncbi Calcium signalling: dynamics, homeostasis and remodelling
    Michael J Berridge
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    Nat Rev Mol Cell Biol 4:517-29. 2003
    ..Ca2+ has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease...
  3. ncbi The versatility and universality of calcium signalling
    M J Berridge
    The Babraham Institute, Laboratory of Molecular Signalling, Babraham Hall, Babraham, Cambridge, CB2 4AT, UK
    Nat Rev Mol Cell Biol 1:11-21. 2000
    ..Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis...
  4. pmc STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx
    Jen Liou
    Department of Molecular Pharmacology, Stanford University Medical School, California 94305, USA
    Curr Biol 15:1235-41. 2005
    ..Our study suggests that STIM proteins function as Ca(2+) store sensors in the signaling pathway connecting Ca(2+) store depletion to Ca(2+) influx...
  5. ncbi A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function
    Stefan Feske
    The CBR Institute for Biomedical Research, and the Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 441:179-85. 2006
    ..We propose that Orai1 is an essential component or regulator of the CRAC channel complex...
  6. pmc Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
    Joshua M Baughman
    Department of Systems Biology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nature 476:341-5. 2011
    ..Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca(2+) uniporter...
  7. pmc STIM1, an essential and conserved component of store-operated Ca2+ channel function
    Jack Roos
    Torrey Pines Therapeutics, Inc, La Jolla, CA 92037, USA
    J Cell Biol 169:435-45. 2005
    ..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels...
  8. ncbi Store-operated calcium channels
    Anant B Parekh
    Department of Physiology, University of Oxford, United Kingdom
    Physiol Rev 85:757-810. 2005
    ....
  9. pmc A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
    Diego De Stefani
    Department of Biomedical Science, University of Padua, 35121 Padua, Italy
    Nature 476:336-40. 2011
    ....
  10. ncbi Orai1 is an essential pore subunit of the CRAC channel
    Murali Prakriya
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Nature 443:230-3. 2006
    ..These changes in ion selectivity provide strong evidence that Orai1 is a pore subunit of the CRAC channel...
  11. ncbi ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures
    Gina M Story
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell 112:819-29. 2003
    ..Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol...
  12. ncbi CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry
    M Vig
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 312:1220-3. 2006
    ..Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery...
  13. ncbi Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1
    Sven Eric Jordt
    Department of Cellular and Molecular Pharmacology University of California, San Francisco, California 94143 2140, USA
    Nature 427:260-5. 2004
    ..These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors...
  14. ncbi Calcium channels in the development, maturation, and function of spermatozoa
    Alberto Darszon
    Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Cuernavaca, Morelos, Mexico
    Physiol Rev 91:1305-55. 2011
    ....
  15. ncbi The mitochondrial calcium uniporter is a highly selective ion channel
    Yuriy Kirichok
    Howard Hughes Medical Institute, Department of Cardiovascular Research, Children s Hospital, andHarvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 427:360-4. 2004
    ..The channel is inwardly rectifying, making it especially effective for Ca2+ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU...
  16. pmc Inositol trisphosphate receptor Ca2+ release channels
    J Kevin Foskett
    Department of Physiology, University of Pennsylvania, Philadelphia 19104 6085, USA
    Physiol Rev 87:593-658. 2007
    ..Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R...
  17. pmc STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1
    Chan Young Park
    Department of Neurobiology, Stanford University School of Medicine, CA 94305, USA
    Cell 136:876-90. 2009
    ..These studies establish a molecular mechanism for store-operated Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions...
  18. ncbi Inositol trisphosphate and calcium signalling
    M J Berridge
    AFRC Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, UK
    Nature 361:315-25. 1993
    ..This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex ..
  19. ncbi Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses
    R Rizzuto
    Department of Biomedical Sciences and the National Research Council Center for the Study of Biomembranes, University of Padova, Via Colombo 3, 35121 Padova, Italy
    Science 280:1763-6. 1998
    ..These results emphasize the importance of cell architecture and the distribution of organelles in regulation of Ca2+ signaling...
  20. pmc The CatSper channel: a polymodal chemosensor in human sperm
    Christoph Brenker
    Center of Advanced European Studies and Research caesar, Abteilung Molekulare Neurosensorik, Bonn, Germany
    EMBO J 31:1654-65. 2012
    ..We propose that the CatSper channel complex serves as a polymodal sensor for multiple chemical cues that assist sperm during their voyage across the female genital tract...
  21. ncbi International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280, USA
    Pharmacol Rev 57:411-25. 2005
    The family of voltage-gated calcium channels serves as the key transducers of cell surface membrane potential changes into local intracellular calcium transients that initiate many different physiological events...
  22. ncbi A sperm ion channel required for sperm motility and male fertility
    D Ren
    Howard Hughes Medical Institute, Children s Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 413:603-9. 2001
    ..CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women...
  23. pmc NAADP mobilizes calcium from acidic organelles through two-pore channels
    Peter J Calcraft
    Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK
    Nature 459:596-600. 2009
    ..TPCs therefore provide new insights into the regulation and organization of Ca(2+) signals in animal cells, and will advance our understanding of the physiological role of NAADP...
  24. ncbi Progesterone activates the principal Ca2+ channel of human sperm
    Polina V Lishko
    Department of Physiology, University of California San Francisco, UCSF Mail Code 2140, Genentech Hall Room N272F, 600 16th Street, San Francisco, California 94158, USA
    Nature 471:387-91. 2011
    ....
  25. pmc TRPA1 mediates formalin-induced pain
    Colleen R McNamara
    Hydra Biosciences, Inc, 790 Memorial Drive, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:13525-30. 2007
    ....
  26. ncbi A TRP channel that senses cold stimuli and menthol
    Andrea M Peier
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
    Cell 108:705-15. 2002
    ..Our identification of a cold-sensing TRP channel in a distinct subpopulation of sensory neurons implicates an expanded role for this family of ion channels in somatic sensory detection...
  27. pmc Voltage-gated calcium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    Cold Spring Harb Perspect Biol 3:a003947. 2011
    ..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties...
  28. ncbi Transient receptor potential channels as therapeutic targets
    Magdalene M Moran
    Hydra Biosciences, 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Nat Rev Drug Discov 10:601-20. 2011
    ..This Review focuses on recent developments in the TRP channel-related field, and highlights potential opportunities for therapeutic intervention...
  29. ncbi The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
    Timo Strünker
    Center of Advanced European Studies and Research, Abteilung Molekulare Neurosensorik, Ludwig Erhard Allee 2, 53175 Bonn, Germany
    Nature 471:382-6. 2011
    ..The identification of CatSper channel blockers will greatly facilitate the study of Ca(2+) signalling in sperm and help to define further the physiological role of progesterone and CatSper...
  30. ncbi Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release
    Robert J Kittel
    European Neuroscience Institute Göttingen, Grisebachstrasse 5, 37077 Gottingen, Germany
    Science 312:1051-4. 2006
    ..BRP-like proteins seem to establish proximity between Ca2+ channels and vesicles to allow efficient transmitter release and patterned synaptic plasticity...
  31. pmc Subunit counting in membrane-bound proteins
    Maximilian H Ulbrich
    Department of Molecular and Cell Biology, University of California, Berkeley Material Science and Physical Bioscience Divisions, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Nat Methods 4:319-21. 2007
    ..After testing the method with proteins of known stoichiometry expressed in Xenopus laevis oocytes, we resolved the composition of NMDA receptors composed of NR1 and NR3 subunits...
  32. pmc Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling
    Eugen Brailoiu
    Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    J Cell Biol 186:201-9. 2009
    ..NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear...
  33. pmc Molecular basis of calcium signaling in lymphocytes: STIM and ORAI
    Patrick G Hogan
    Department of Pathology, Harvard Medical School, Immune Disease Institute, Children s Hospital Boston, Massachusetts 02115, USA
    Annu Rev Immunol 28:491-533. 2010
    ..In this review, we discuss selected aspects of Ca(2+) signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca(2+) entry...
  34. pmc Gated regulation of CRAC channel ion selectivity by STIM1
    Beth A McNally
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University School of Medicine, 303 E Chicago Avenue, Ward 8 296, Chicago, Illinois 60611, USA
    Nature 482:241-5. 2012
    ..Our results demonstrate that STIM1-mediated gating of CRAC channels occurs through an unusual mechanism in which permeation and gating are closely coupled...
  35. pmc Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity
    Shenyuan L Zhang
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 103:9357-62. 2006
    ....
  36. ncbi Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors
    Kimiko Kobayashi
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663 8501, Japan
    J Comp Neurol 493:596-606. 2005
    ....
  37. pmc Calcium channels and pumps in cancer: changes and consequences
    Gregory R Monteith
    School of Pharmacy, The University of Queensland, Brisbane 4075, Australia
    J Biol Chem 287:31666-73. 2012
    ..In some cases, these Ca(2+) channels or pumps are potential therapeutic targets for specific cancer subtypes or correlate with prognosis...
  38. pmc K+ channels as targets for specific immunomodulation
    K George Chandy
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Trends Pharmacol Sci 25:280-9. 2004
    ..3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders...
  39. ncbi Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain
    Shenglan Wang
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1 1 Mukogawa cho, Nishinomiya, Hyogo 663 8501, Japan
    Brain 131:1241-51. 2008
    ..Collectively, these results represent a novel mechanism through which bradykinin released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation...
  40. ncbi CRACM1 multimers form the ion-selective pore of the CRAC channel
    Monika Vig
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Curr Biol 16:2073-9. 2006
    ..Our data provide unequivocal evidence that CRACM1 multimers form the Ca(2+)-selective CRAC-channel pore...
  41. pmc TRP channel activation by reversible covalent modification
    Andrew Hinman
    Department of Physiology, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 103:19564-8. 2006
    ..These findings suggest an unusual paradigm whereby natural products activate a receptor through direct, reversible, and covalent protein modification...
  42. pmc Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis
    Cagla Eroglu
    Duke University Medical Center, Cell Biology Department, Durham, NC 27710, USA
    Cell 139:380-92. 2009
    ..These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation...
  43. ncbi Identification of a cold receptor reveals a general role for TRP channels in thermosensation
    David D McKemy
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143 0450, USA
    Nature 416:52-8. 2002
    ....
  44. pmc Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel
    Michael R Tadross
    Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Cell 133:1228-40. 2008
    ..The emergence of complex decoding properties from the juxtaposition of common elements, and the techniques developed herein, promise generalization to numerous molecules residing near Ca(2+) sources...
  45. ncbi Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel
    Yuriy Kirichok
    Howard Hughes Medical Institute, Department of Cardiology, Children s Hospital and Harvard Medical School Enders 1309, Boston, Massachusetts 02115, USA
    Nature 439:737-40. 2006
    ..Our results identify CatSper1 as a component of the key flagellar calcium channel, and suggest that intracellular alkalinization potentiates CatSper current to increase intraflagellar calcium and induce sperm hyperactivation...
  46. ncbi Orai1 and STIM1 are critical for breast tumor cell migration and metastasis
    Shengyu Yang
    Department of Physiology, Weill Medical College of Cornell University, New York, NY 10065, USA
    Cancer Cell 15:124-34. 2009
    ..highly metastatic human breast cancer cells or treatment with a pharmacological inhibitor of store-operated calcium channels decreased tumor metastasis in animal models...
  47. pmc Subunit stoichiometry of human Orai1 and Orai3 channels in closed and open states
    Angelo Demuro
    Department of Neurobiology and Behavior, Institute for Immunology, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:17832-7. 2011
    ..We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB...
  48. ncbi Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
    L Chen
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA
    Nature 408:936-43. 2000
    ....
  49. pmc mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state
    Chunlei Cang
    Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA
    Cell 152:778-90. 2013
    ..Thus, TPCs make up an ion channel family that couples the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction...
  50. pmc Ca2+ signals generated by CatSper and Ca2+ stores regulate different behaviors in human sperm
    Wardah Alasmari
    From the Reproductive and Developmental Biology, Medical School, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 288:6248-58. 2013
    ....
  51. pmc The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from lysosomal stores
    Xiangang Zong
    Center for Integrated Protein Science CIPS M and Zentrum für Pharmaforschung, Department Pharmazie, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, 81377, Munich, Germany
    Pflugers Arch 458:891-9. 2009
    ..By contrast, TPCN2-specific Ca(2+)-release is unaffected by emptying ER-based Ca(2+) stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca(2+)-release channel...
  52. pmc Pungent products from garlic activate the sensory ion channel TRPA1
    Diana M Bautista
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 102:12248-52. 2005
    ..Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence...
  53. ncbi Calcium channel regulation and presynaptic plasticity
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Neuron 59:882-901. 2008
    ..We propose that presynaptic Ca(2+) channels serve as the regulatory node in a dynamic, multilayered signaling network that exerts short-term control of neurotransmission in response to synaptic activity...
  54. pmc Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation
    Riina M Luik
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 454:538-42. 2008
    ....
  55. ncbi 2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release
    Martin D Bootman
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    FASEB J 16:1145-50. 2002
    ..These data indicate that although it must be used with caution, 2-APB can be useful in probing certain aspects of Ca2+ signaling...
  56. ncbi Two newly identified genetic determinants of pigmentation in Europeans
    Patrick Sulem
    deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
    Nat Genet 40:835-7. 2008
    ....
  57. pmc Internal Ca(2+) release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue
    Valerie Denis
    Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA
    J Cell Biol 156:29-34. 2002
    ..These studies reveal a novel mechanism of internal Ca(2+) release and establish a new function for TRP channels...
  58. ncbi Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences
    S Ghanshani
    Department of Physiology and Biophysics, and Department of Microbiology and Molecular Genetics, University of California, Irvine, California 92697, USA
    J Biol Chem 275:37137-49. 2000
    ..Thus, Kv1.3 channels are essential for activation of quiescent cells, but signaling through the PKC pathway enhances expression of IKCa1 channels that are required for continued proliferation...
  59. pmc Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis
    Yih Fung Chen
    Department of Pharmacology, National Cheng Kung University, Tainan 70101, Taiwan
    Proc Natl Acad Sci U S A 108:15225-30. 2011
    ..These results make STIM1-dependent signaling an attractive target for therapeutic intervention...
  60. pmc 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1
    Marcello Trevisani
    Department of Critical Care Medicine and Surgery, Florence University, 4 50121 Florence, Italy
    Proc Natl Acad Sci U S A 104:13519-24. 2007
    ..Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation...
  61. ncbi STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels
    Guo N Huang
    Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Nat Cell Biol 8:1003-10. 2006
    ..These observations implicate STIM1 as a key regulator of activity rather than a channel component, and reveal similar regulation of SOC, I(crac) and TRPC channel activation by STIM1...
  62. ncbi Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol
    T Hofmann
    Institut fur Pharmakologie, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany
    Nature 397:259-63. 1999
    ..Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol...
  63. ncbi TRP channels as cellular sensors
    David E Clapham
    Howard Hughes Medical Institute, Pediatric Cardiology, Children s Hospital of Boston, Department of Neurobiology, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 426:517-24. 2003
    ..They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell...
  64. ncbi Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand
    Ivan Bosanac
    Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Nature 420:696-700. 2002
    ..Putative Ca2+-binding sites are identified in two separate locations within the InsP3-binding core...
  65. pmc A Cytosolic Homomerization and a Modulatory Domain within STIM1 C Terminus Determine Coupling to ORAI1 Channels
    Martin Muik
    Institute of Biophysics, University of Linz, A 4040 Linz
    J Biol Chem 284:8421-6. 2009
    ....
  66. pmc Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels
    Monika Vig
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 9:89-96. 2008
    CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release-activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans...
  67. pmc SOAR and the polybasic STIM1 domains gate and regulate Orai channels
    Joseph P Yuan
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Nat Cell Biol 11:337-43. 2009
    ..Hence, the essential properties of Orai1 function can be rationalized by interactions with discrete regions of STIM1...
  68. pmc 2-Aminoethoxydiphenyl borate directly facilitates and indirectly inhibits STIM1-dependent gating of CRAC channels
    Christine Peinelt
    Queen s Medical Center and John A Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
    J Physiol 586:3061-73. 2008
    ....
  69. pmc Mutations in Orai1 transmembrane segment 1 cause STIM1-independent activation of Orai1 channels at glycine 98 and channel closure at arginine 91
    Shenyuan L Zhang
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:17838-43. 2011
    ..We propose distinct functional roles for G98 as a gating hinge and R91 as part of the physical gate at the narrow inner mouth of the channel...
  70. pmc A novel native store-operated calcium channel encoded by Orai3: selective requirement of Orai3 versus Orai1 in estrogen receptor-positive versus estrogen receptor-negative breast cancer cells
    Rajender K Motiani
    Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208, USA
    J Biol Chem 285:19173-83. 2010
    ..Future studies implicating Orai3 in ER(+) breast cancer progression might establish Orai3 as a selective target in therapy of ER(+) breast tumors...
  71. pmc CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm
    Anne E Carlson
    Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:14864-8. 2003
    ..We propose that CatSper1 functions as a voltage-gated Ca2+ channel that controls Ca2+ entry to mediate the hyperactivated motility needed late in the preparation of sperm for fertilization...
  72. pmc Store-independent activation of Orai1 by SPCA2 in mammary tumors
    Mingye Feng
    Department of Physiology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Cell 143:84-98. 2010
    ..Our findings reveal a signaling pathway in which the Orai1-SPCA2 complex elicits constitutive store-independent Ca(2+) signaling that promotes tumorigenesis...
  73. ncbi Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs
    Susumu Tomita
    Department of Physiology, University of California at San Francisco, San Francisco, CA 94143, USA
    Neuron 45:269-77. 2005
    ..These results establish stargazin as a critical substrate in the bidirectional control of synaptic strength, which is thought to underlie aspects of learning and memory...
  74. ncbi Voltage-gated calcium channels in genetic diseases
    Isabelle Bidaud
    Departement de Physiologie, Institut de Génomique Fonctionnelle IGF, CNRS UMR 5203 INSERM U661, Universités de Montpellier I and II, 141 rue de la Cardonille, 34094 Montpellier Cedex 05, France
    Biochim Biophys Acta 1763:1169-74. 2006
    Voltage-gated calcium channels (VGCCs) mediate calcium entry into excitable cells in response to membrane depolarization...
  75. pmc TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes
    Xiang Wang
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 3089 Kraus Natural Science Building, 830 North University Avenue, Ann Arbor, MI 48109, USA
    Cell 151:372-83. 2012
    ..These findings suggest that the organellar membrane potential may undergo large regulatory changes and may explain the specificity of PI(3,5)P(2) in regulating the fusogenic potential of intracellular organelles...
  76. ncbi Estrogen controls embryonic stem cell proliferation via store-operated calcium entry and the nuclear factor of activated T-cells (NFAT)
    Chun Kit Wong
    School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China
    J Cell Physiol 227:2519-30. 2012
    ..Previous studies showed that store-operated calcium channels (SOCCs) but not voltage-operated calcium channels are present in mouse ESCs (mESCs)...
  77. ncbi Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in breast cancer cells but not in normal breast epithelial cells
    Malika Faouzi
    Laboratoire de Physiologie Cellulaire et Moleculaire, JE 2530 Canaux Ioniques dans le cancer du sein, Faculte des Sciences, UPJV, Amiens, France
    J Cell Physiol 226:542-51. 2011
    ..Our study highlights a possible role of Orai3 as therapeutic target in BC therapy...
  78. pmc Photoaffinity labeling of nicotinic acid adenine dinucleotide phosphate (NAADP) targets in mammalian cells
    Yaping Lin-Moshier
    Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    J Biol Chem 287:2296-307. 2012
    ..This observation necessitates critical evaluation of current models of NAADP-triggered activation of the TPC family...
  79. ncbi Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44
    Takayasu Higo
    Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Cell 120:85-98. 2005
    ..Thus, ERp44 senses the environment in the ER lumen and modulates IP(3)R1 activity accordingly, which should in turn contribute to regulating both intralumenal conditions and the complex patterns of cytosolic Ca(2+) concentrations...
  80. pmc Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation
    Jing Li
    Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    Circ Res 108:1190-8. 2011
    ..Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown...
  81. ncbi Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL
    S Chyb
    Cambridge University Department of Anatomy, UK
    Nature 397:255-9. 1999
    ..As arachidonic acid may not be found in Drosophila, we suggest that another polyunsaturated fatty acid, such as linolenic acid, may be a messenger of excitation in Drosophila photoreceptors...
  82. pmc Cch1 restores intracellular Ca2+ in fungal cells during endoplasmic reticulum stress
    Min Pyo Hong
    Department of Pharmacology, School of Medicine, University of California, Davis, California 95616, USA
    J Biol Chem 285:10951-8. 2010
    ..The inability of cryptococcal cells that lacked the Cch1-Mid1 channel to survive ER stress suggests that Cch1 and its co-regulator, Mid1, are critical players in the restoration of Ca(2+) homeostasis...
  83. pmc The control of male fertility by spermatozoan ion channels
    Polina V Lishko
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Annu Rev Physiol 74:453-75. 2012
    ..The uniqueness of sperm ion channels makes them ideal pharmaceutical targets for contraception. In this review we discuss how ion channels regulate sperm physiology...
  84. pmc Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels
    Yanhong Liao
    Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 105:2895-900. 2008
    ..We propose that SOCE/Icrac channels are composed of heteromeric complexes that include TRPCs and Orai proteins...
  85. pmc An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals
    Eugen Brailoiu
    Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 285:38511-6. 2010
    ..We therefore uncouple TPC2 from amplification pathways and prove that it is a pore-forming subunit of an NAADP-gated Ca(2+) channel...
  86. ncbi The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function
    Anthony Davies
    Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Neurosci 26:8748-57. 2006
    The accessory alpha2delta subunits of voltage-gated calcium channels are highly glycosylated transmembrane proteins that interact with calcium channel alpha1 subunits to enhance calcium currents...
  87. pmc The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels
    Youjun Wang
    Department of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA
    Science 330:105-9. 2010
    ..2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed Ca(V)1...
  88. ncbi TRPC1 and TRPC5 form a novel cation channel in mammalian brain
    C Strübing
    Howard Hughes Medical Institute, Cardiovascular Research, Children s Hospital, 320 Longwood Avenue, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
    Neuron 29:645-55. 2001
    ..In contrast to the more common view of the TRP family as comprising store-operated channels, we propose that many TRPC heteromers form diverse receptor-regulated nonselective cation channels in the mammalian brain...
  89. ncbi Impairment of store-operated Ca2+ entry in TRPC4(-/-) mice interferes with increase in lung microvascular permeability
    Chinnaswamy Tiruppathi
    Department of Pharmacology, College of Medicine, The University of Illinois, Chicago, Ill 60612, USA
    Circ Res 91:70-6. 2002
    ..These results show that TRPC4-dependent Ca2+ entry in mouse LECs is a key determinant of increased microvascular permeability...
  90. ncbi The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel
    A Ducros
    INSERM E99 21, Faculté de Médecine Lariboisiere, Paris, France
    N Engl J Med 345:17-24. 2001
    ..We studied the various clinical manifestations associated with mutations in CACNA1A in families with hemiplegic migraine with and without cerebellar signs...
  91. pmc Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels
    Paul T Mungai
    Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Mol Cell Biol 31:3531-45. 2011
    ..attenuates the calcium responses to hypoxia and subsequent AMPK phosphorylation, while inhibition of L-type calcium channels has no effect...
  92. pmc Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents
    Eunice Andre
    Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy
    J Clin Invest 118:2574-82. 2008
    ..These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases...
  93. ncbi Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction
    C Montell
    Howard Hughes Medical Institute, University of California, Berkeley 94720
    Neuron 2:1313-23. 1989
    ..Immunolocalization indicates that the trp protein is expressed predominantly in the rhabdomeric membranes of the photoreceptor cells...
  94. ncbi CRACM1, CRACM2, and CRACM3 are store-operated Ca2+ channels with distinct functional properties
    Annette Lis
    Center for Biomedical Research, The Queen s Medical Center, Honolulu, Hawaii 96813, USA
    Curr Biol 17:794-800. 2007
    ....
  95. pmc HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity
    Samer R Eid
    Department of Pain Research, Neuroscience Drug Discovery, Merck Research Laboratories, West Point, Philadelphia, USA
    Mol Pain 4:48. 2008
    ..The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain...
  96. ncbi Calcium and cancer: targeting Ca2+ transport
    Gregory R Monteith
    School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia, 4072
    Nat Rev Cancer 7:519-30. 2007
    ..This Review presents evidence to the contrary and addresses the question: which Ca2+ channels and pumps should be targeted?..
  97. pmc A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels
    Ivy E Dick
    Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nature 451:830-4. 2008
    ..Finally, the modularity of NSCaTE offers practical means for understanding the basis of global Ca2+ selectivity...
  98. pmc CaV2.3 calcium channels control second-phase insulin release
    Xingjun Jing
    Diabetes Programme at Lund University, Lund, Sweden
    J Clin Invest 115:146-54. 2005
    ..3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation...
  99. ncbi Calcium microdomains: organization and function
    Michael J Berridge
    Babraham Institute, Babraham, Cambridge, UK
    Cell Calcium 40:405-12. 2006
    ..Control of cardiac cell contraction and gene transcription provides another example of how the parallel processing of Ca(2+) signalling can occur through microdomains of intracellular Ca(2+)...
  100. ncbi Ca2+ hot spots on the mitochondrial surface are generated by Ca2+ mobilization from stores, but not by activation of store-operated Ca2+ channels
    Marta Giacomello
    Department of Biomedical Sciences, University of Padova, Padova, Italy
    Mol Cell 38:280-90. 2010
    ..These results demonstrate that mitochondria are exposed to Ca(2+) hot spots close to the ER but are excluded from the regions where capacitative Ca(2+) influx occurs...
  101. ncbi IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism
    Akira Futatsugi
    Calcium Oscillation, International Cooperative Research Project, Japan Science and Technology Agency, Tokyo 108 0071, Japan
    Science 309:2232-4. 2005
    ..Despite a normal caloric intake, the double mutants were hypoglycemic and lean. These results reveal IP3R2 and IP3R3 as key molecules in exocrine physiology underlying energy metabolism and animal growth...

Research Grants71

  1. Principles of Therapy in Cerebellar Disease: Explorations in Ion Channel Mutants
    JOHN SAMUEL STAHL; Fiscal Year: 2013
    ..on the cerebellar disorders arising from mutations of the genes that specify the structure of neuronal calcium channels, because: 1) Such "channelopathy" diseases form one of the largest groups of heritable, degenerative, ..
  2. Right ventricular contractile dysfunction after pressure overload
    CLIFFORD RUSSELL GREYSON; Fiscal Year: 2013
    ..Agents with potential clinical utility will be identified using the isolated papillary muscle model and tested in the pig model. ..
  3. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    ..We propose to study the cell biology and physiology of K-Ras phosphorylation to better understand how to exploit this process to develop anti-cancer drugs. ..
  4. Ionic currents in gastrointestinal smooth muscle
    Hamid I Akbarali; Fiscal Year: 2013
    ..Determining the mechanisms of altered protein-protein interaction between ion channels and intracellular signaling molecules are likely to define novel therapeutic approaches targeted at ion channels ..
  5. Reversing Corticosteroid-Induced Memory Impairment
    E Sherwood Brown; Fiscal Year: 2013
    ..and bipolar disorder medication that decreases glutamate release through interactions with sodium and calcium channels. We conducted both open-label and placebo-controlled trials of lamotrigine in corticosteroid-treated patients ..
  6. IDENTIFICATION OF ACOUSTICO-LATERALIS TRANSMITTERS
    Dennis G Drescher; Fiscal Year: 2013
    ..Molecular interactions of hair cell voltage-gated calcium channels (VGCC) with synaptic proteins and with scaffolding proteins will be investigated...
  7. NIH Director's Pioneer Award
    Karl Deisseroth; Fiscal Year: 2009
    ..abstract_text> ..
  8. Molecular physiology of voltage-gated Ca2+ channels
    Jian Yang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Voltage-gated calcium channels (VGCCs) control and regulate numerous physiological processes, ranging from muscle contraction, heartbeat, neural communication and hormone secretion to cell ..
  9. Functional Studies of Variants of the Bipolar Risk Gene CACNA1C in Human Neurons
    JEN PAN; Fiscal Year: 2013
    ....
  10. TRP channels in regulation of vascular tone
    David X Zhang; Fiscal Year: 2013
    ....
  11. Mineralocorticoid Receptor-Mediated Vascular Insulin Resistance
    SHAWN BRADY BENDER; Fiscal Year: 2013
    ..IR will be induced in wild-type and VSMC MR KO mice with a high-fat, high-sucrose diet and will be assessed by glucose tolerance testing. ..
  12. Spinocerebellar Ataxia Type 2 Gene and Gene Product
    Stefan M Pulst; Fiscal Year: 2012
    ..This will allow us to test the effects of specific proteins on nerve cell dysfunction and cell death in live animals with the ultimate goal of identifying new therapeutic avenues for treatment of human neurodegenerative diseases. ..
  13. Epigenetic regulation in neuropathic pain
    Zhonghui Guan; Fiscal Year: 2013
    ..My department has guaranteed lab space and 80% of my professional time for my research, neither of which is contingent upon my receipt of this career award. ..
  14. The role of trace metals and T-channels in pain
    Slobodan M Todorovic; Fiscal Year: 2013
    ..Recent studies have established that CaV3.2 T- type voltage-gated calcium channels (T-channels) play a key role in control of cellular excitability of peripheral nociceptors and thus represent ..
  15. The Role of CRACM1 in the Pathogenesis of Systemic Lupus Erythematosus
    Peter C Chien; Fiscal Year: 2013
    ..abstract_text> ..
  16. Mechanisms and translation of lipid resuscitation
    Guy L Weinberg; Fiscal Year: 2013
    ..Improved patient safety and outcomes from drug toxicity are the over-arching goals of this project. ..
  17. Reciprocal Control of Ca2+ Channels by Anchored Protein Kinase A and Calcineurin
    William A Sather; Fiscal Year: 2010
    ..Relevance to Public Health. Calcium channels help control activity of nerve cells, beating of heart cells, contraction of smooth muscle cells that are ..
  18. The role of NFAT in podocyte damage and proteinuric kidney disease
    ALEXIS JOANNA SLOAN; Fiscal Year: 2013
    ..Gain of function mutations in TRCP6 calcium channels can lead to alterations in proper podocyte morphology and the loss of the glomerular filter leading to loss ..
  19. Chronic stress-induced gene expression in colonic circular smooth muscle cells.
    Sushil K Sarna; Fiscal Year: 2012
    ..2 (L-type) calcium channels, leading to reduced Ca2+ influx and cell contractility...
  20. Acquisition of a TIRF/Widefield fluorescence microscope for cell biology and neur
    Bryon D Grove; Fiscal Year: 2013
    ..function in amyloidogenesis associated with Alzheimer's disease, 2) investigate the role of TRPC calcium channels and dysregulation of calcium homeostasis in dopaminergic neuronal cell death associated with Parkinson[..
  21. Comparative safety &effectiveness of antihypertensive medications in pregnancy
    BRIAN THOMAS BATEMAN; Fiscal Year: 2013
    ..This combination of intensive research, mentoring, and formal education will provide the necessary background for me to become a successful, independent researcher in obstetric pharmacoepidemiology. ..
  22. MRP4 extrudes cAMP for localized regulation of calcium channel activity
    OLIVIA RUTH BUONARATI; Fiscal Year: 2013
    ..2-associated disorders in the central nervous system, including stroke, depression, anxiety, senility and Alzheimer's disease. ..
  23. DEPOLARIZATION-SECRETION COUPLING IN NERVE TERMINALS
    Jose R Lemos; Fiscal Year: 2012
    ..Only then can therapeutic drugs be targeted to physiologically relevant purinergic receptors to alleviate such diseases. ..
  24. Udall Parkinson's Disease Center at Emory University: Circuitry to Therapy
    THOMAS N WICHMANN; Fiscal Year: 2013
    ....
  25. Calcium Signaling, Metabolism, and EC Coupling in Heart
    Joshua I Goldhaber; Fiscal Year: 2013
    ..This will include a measurement of the minimum number of L-type calcium channels in a couplon and the way that metabolic inhibition affects their function...
  26. Neuron-specific block of T-type calcium channels
    Edward Perez-Reyes; Fiscal Year: 2012
    ..The research team includes Dr. Edward Perez- Reyes, a T-channel expert, Dr. Guanping Gao, an AAV expert, and Dr. Hui-Lin Pan, a neuropathic pain expert. ..
  27. The exocyst in ciliogenesis and cystogenesis
    Joshua H Lipschutz; Fiscal Year: 2013
    ..Here, we propose experiments to test how the exocyst builds primary cilia, with successful completion leading to identification of novel candidate targets for intervention in ADPKD. ..
  28. Nitrergic Neuro-smooth Muscle Transmission in the Gut
    Raj K Goyal; Fiscal Year: 2013
    ..3) To investigate the clustering of nNOS-PSD complex with N-type calcium channels and the enzymes that dephosphorylate or phosphorylate nNOS and to investigate the effects of inhibitors of ..
  29. Reduced contractile reserve: a therapeutic target in heart failure with normal EF
    Nancy K Sweitzer; Fiscal Year: 2012
    ..This project explores the underlying cardiovascular physiology of patients with HFpEF with the goal of identifying new therapeutic targets that would allow improved treatment of this devastating disease. ..
  30. FKBP Interaction with RYR Calcium Channels in Heart
    Donald M Bers; Fiscal Year: 2013
    ..We will conduct fundamental quantitative molecular fluorescence studies that will clarify both structurally and functionally how FKBP binds to and regulates RyR function in the heart. ..
  31. Regulation of Cardiac Calcium Channels by an Autoinhibitory Signalling Complex
    William A Catterall; Fiscal Year: 2013
    ..These studies will increase understanding of regulation of the heart by the sympathetic nervous system and give essential new insight into the molecular and functional changes in the Cav1.2 signaling complex in heart failure. ..
  32. Astrocyte dysfunction in EAE
    David N Irani; Fiscal Year: 2012
    ..1) To confirm the importance of astrocyte-derived TSP- 1/TSP-2 signaling through neuronal a2d-1 voltage-gated calcium channels in mediating the reversible paralysis of relapsing EAE by acting on excitatory synapses in motor pathways of ..
  33. 3D Structure and Function of CRAC Channels
    STEPHEN BARSTOW LONG; Fiscal Year: 2013
    ....
  34. LISTERIA AND SHIGELLA USE ACTIN TO SPREAD CELL TO CELL
    Frederick Southwick; Fiscal Year: 2013
    ..These discoveries can be applied to all forms of cell motility, including tumor metastasis, neurite outgrowth, and platelet spreading. ..
  35. STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
    Adrian Gross; Fiscal Year: 2013
    ..of structurally related ion channels that includes nucleotide gated channels, sodium channels, and calcium channels. Potassium channels are typically assembled from four identical subunits in a four-fold symmetrical fashion...
  36. Estrogen Modulation of Bursting Activity in GnRH Neurons
    Oline K Ronnekleiv; Fiscal Year: 2013
    ..kisspeptin that increase TRPC channel activity in GnRH neurons;and (4) elucidate the E2 regulation of T-type calcium channels in GnRH neurons using the mER ligand STX...
  37. Caveolae and mitochondria: A structural interface functionally linking calcium an
    GREGORY CHARLES AMBERG; Fiscal Year: 2013
    ..A major source of calcium entry into these cells is through voltage-dependent L-type calcium channels. The general goal of this proposal is to investigate the poorly understood mechanisms controlling calcium ..
  38. Calcium channels in arterial smooth muscle cells
    Jonathan H Jaggar; Fiscal Year: 2013
    ..2 channels are expressed in arterial smooth muscle cells, and that the molecular composition of these channels is altered in hypertension, leading to vasoconstriction. ..
  39. Enteric Virus Calcium Channel Inhibitors
    Joseph M Hyser; Fiscal Year: 2013
    ..The data and techniques in these studies will form the basis of my independent research program on viral calcium channels and development of viroporin inhibitors as tools for molecular virology studies and leads for antiviral drug ..
  40. Mechanisms of Alcohol Withdrawal
    Dwayne W Godwin; Fiscal Year: 2012
    ..These bursts depend upon a class of T-type calcium channels that are expressed within the brain and periphery...
  41. Functional immuno-imaging of lymphocyte motility and cell interactions in lymph n
    Michael D Cahalan; Fiscal Year: 2013
    ..The second goal is to investigate immunosuppression mediated by blockade of specific ion channels in T lymphocytes - a potassium channel Kv1.3 and a calcium channel Orai1 - for treatment of autoimmune disorders. ..
  42. Molecular Biology of Marfan Syndrome
    Harry C Dietz; Fiscal Year: 2013
    ..These studies have the strong potential to unveil novel therapeutic targets and strategies for MFS and perhaps more common presentations of aneurysm. ..
  43. Functional interactions among retinoschisin and its binding partners
    GLADYS Y KO; Fiscal Year: 2013
    ..Impact: This research program will reveal how retinoschisin interacts with its binding partners, specifically L-VGCCs and PMCA1, and new roles of retinoschisin in photoreceptor physiology and function. ..
  44. Longitudinal Impact of Antihypertensive Polypharmacy on Geriatric Syndromes
    Joseph T Hanlon; Fiscal Year: 2012
    ..e., blood pressure control), and morbidity and mortality (i.e., hospitalization and death due to cardiovascular and cerebrovascular disease). Such studies are consistent with NIA's priority comparative effectiveness research area. ..
  45. Gonadal Hormones and Depression:The Role of Mood Disorder Risk Gene CACNA1C
    Todd D Gould; Fiscal Year: 2012
    ....
  46. T-type Calcium Channels and Aldosterone Secretion
    Paula Q Barrett; Fiscal Year: 2013
    ....
  47. Lipidomic profile of endocannabinoids from neuronal cells
    VINCENT JO DAVISSON; Fiscal Year: 2010
    ..The specific metabolic and biosynthetic pathways linked to certain calcium channels as well as neurotransmitter receptor activation will be explored...
  48. Mechanisms of permeation and gating of voltage-sensing domains
    Francesco Tombola; Fiscal Year: 2013
    ..proton channel Hv1, a protein that lacks the pore domain typical of voltage-gated sodium, potassium, and calcium channels and conducts protons through its VSD...
  49. Chemical Biology of Mitochondria and Diabetes
    Bruce M Spiegelman; Fiscal Year: 2013
    ..abstract_text> ..
  50. PRESYNAPTIC LONG-TERM SYNAPTIC DEPRESSION
    Patric K Stanton; Fiscal Year: 2012
    ..3) What is the role of G[unreadable][unreadable] binding the synaptic vesicle proteins or voltage-dependent calcium channels in presynaptic terminals in NMDAR- versus mGluR-dependent LTD? There is a probable role for LTD in memory ..
  51. MicroRNA to decrease vascular CaV1.2 in hypertension
    Philip T Palade; Fiscal Year: 2013
    ..2) calcium channels. Notably, CaV1...
  52. The Role of Calcium Signaling in Stem Cell Quiescence
    Gozde Yucel; Fiscal Year: 2010
    ..These data support my hypothesis that calcium transients via the voltage gated calcium channels regulate hair stem cell quiescence through Nfatcl regulation...
  53. Antigen Binding, Crosslinking and Transmembrane Signaling
    David A Holowka; Fiscal Year: 2013
    ..The mechanism for activation of store-operated Ca2+ influx via recently identified Orai1/CRACM1 calcium channels will be characterized using fluorescence resonance energy transfer imaging for measurements of molecular ..
  54. Control of Excitatory Synapse Formation and Maturation by Astrocytes
    WILLIAM CHRISTOPHER RISHER; Fiscal Year: 2013
    ..Better understanding of TSP, a2d-1, hevin and SPARC may lead to improvements in the treatment of neurological diseases such as schizophrenia and autism which are characterized by aberrant synaptic connectivity. ..
  55. Defining Target Contribution to Orofacial Pain by Antisense Oligonucleotides
    Zhigang Luo; Fiscal Year: 2009
    ..Completion of this study will allow us to expand the scope of the parent proposal and accelerate the tempo of scientific research in this under investigated field and the discovery of new drug targets for chronic pain disorders. ..
  56. VIP-induced gene expression in colonic smooth muscle cells
    Sushil K Sarna; Fiscal Year: 2010
    ..The findings will provide genomic and molecular insights into regulation of the expression of L-type calcium channels that play a critical role in excitation-contraction coupling in the normal state and during inflammation...
  57. AKAP Regulation of Neuronal L-type Calcium Channel Signaling to the Nucleus
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ....
  58. Identification of a Stretch-Activated Channel with a Role in Cardiac Development
    Dipayan Chaudhuri; Fiscal Year: 2013
    ..By identifying key molecules that sense blood pressure, we hope to gain new insight into how these diseases develop and establish these sensors as targets for the design of novel drugs. ..
  59. Extrarenal Functions of Polycystin-1
    L Darryl Quarles; Fiscal Year: 2013
    ..In addition, a greater knowledge of polycystins and primary cilia functions in a different cellular context could translate into a broader understanding of their functions in the kidney. ..
  60. Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels
    Kristin Webster; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): L-type CaV1.2 voltage-gated calcium channels are essential for mediating muscle contraction, hormone release from endocrine cells, and activity-dependent gene expression in neurons...
  61. GABA-B Receptor Modulation of Calcium Currents
    Michelle Mynlieff; Fiscal Year: 2010
    ..2 is to determine whether the enhancement of L-type calcium current is through activation of silent L-type calcium channels via a phosphorylation event...
  62. Immunophilins regulate SOC entry channels in pulmonary endothelial cells
    Donna L Cioffi; Fiscal Year: 2013
    ....
  63. The Role of Uromodulin in the Regulation of the Renal Calcium Channel TRPV5
    MATTHIAS TILMANN FLORIAN WOLF; Fiscal Year: 2013
    ..Results obtained by these experiments will improve the knowledge of hypercalciuria, a significant risk factor for kidney stones, and may contribute to the development of novel treatment strategies in nephrolithiasis. ..
  64. INCREASED TESTICULAR CD2+ & INFERTILITY WITH VARICOCELE
    Susan Benoff; Fiscal Year: 2004
    ..Sperm voltage-dependent calcium channels (VDCC) are an apparent entry point for Cd2+ VDCC isoform expression variability correlates with mannose ..
  65. CALCIUM CHANNEL BLOCKERS--KINETICS, ACTION & METABOLISM
    STEPHEN BAI; Fiscal Year: 1992
    ..This information will also be valuable to the pharmacologist by providing insight into possible mechanisms responsible for alterations due to differences in the route of administration and to drug interactions...
  66. Synaptic Defects in the Ca Channel Mutant Mouse
    Kathleen Dunlap; Fiscal Year: 2004
    ..from applicant's abstract) Naturally-occurring mutations in the gene encoding class A (or P/Q-type) calcium channels are associated with multiple abnormalities, ranging from migraine headache to motor ataxias to absence ..
  67. Cardiac Channels: Targets of Drugs that Affect Kinetics
    Dorothy A Hanck; Fiscal Year: 2010
    ..Although they are generally thought to preferentially block L-type calcium channels in the vascular system, some of them have also been reported to block T-type calcium channels as well...
  68. Cerebral artery Ca2+ signaling & subarachnoid hemorrhage
    George Wellman; Fiscal Year: 2009
    ..This study should significantly enhance current knowledge with respect to Ca2+signaling and constriction of cerebral arteries in health and disease and provide insight into possible new therapies for the treatment of cerebral vasospasm. ..
  69. ROLE OF PLASMA MEMBRANE IN STIMULUS-SECRETION COUPLING
    Margarethe Hoenig; Fiscal Year: 1991
    ..Specifically, we wish to accomplish the following: 1) to characterize voltage-dependent calcium channels and study their influence on the intracellular calcium ion concentration and insulin release; 2) to study ..
  70. LTP AND SPATIAL LEARNING
    TIMOTHY TEYLER; Fiscal Year: 2002
    ..This form of LTP is induced by 200 Hz stimulation through voltage dependent calcium channels, and contributes to the LTP observed in typical in vitro and in vivo experiments (i.e. 100 Hz stimulation)...
  71. Lipid modulation of beta-cell calcium channels
    Lina Moitoso de Vargas; Fiscal Year: 2006
    ..Ca2+ was inhibited by dihydropyridines and thus depended on functional L-type (voltage-dependent calcium channels) VDCC...