ion channel gating

Summary

Summary: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.

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. pmc The crystal structure of a voltage-gated sodium channel
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 475:353-8. 2011
  3. ncbi Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 450:376-82. 2007
  4. pmc Crystal structure of a voltage-gated sodium channel in two potentially inactivated states
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 486:135-9. 2012
  5. pmc Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel
    Xu Zhang
    State Key Laboratory of Bio membrane and Membrane Biotechnology, Center for Structural Biology, Tsinghua University, Beijing 100084, China
    Nature 486:130-4. 2012
  6. ncbi Mechanism of voltage gating in potassium channels
    Morten Ø Jensen
    D E Shaw Research, New York, NY 10036, USA
    Science 336:229-33. 2012
  7. ncbi hERG potassium channels and cardiac arrhythmia
    Michael C Sanguinetti
    Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, Utah 84112, USA
    Nature 440:463-9. 2006
  8. 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
  9. pmc Molecular mechanism of ATP binding and ion channel activation in P2X receptors
    Motoyuki Hattori
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 485:207-12. 2012
  10. pmc Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel
    Stephen G Brohawn
    Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 335:436-41. 2012

Detail Information

Publications271 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. pmc The crystal structure of a voltage-gated sodium channel
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 475:353-8. 2011
    ..This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level...
  3. ncbi Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 450:376-82. 2007
    ..The detailed structure, which can be compared directly to a large body of functional data, explains charge stabilization within the membrane and suggests a mechanism for voltage-sensor movements and pore gating...
  4. pmc Crystal structure of a voltage-gated sodium channel in two potentially inactivated states
    Jian Payandeh
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Nature 486:135-9. 2012
    ..These potential inactivated-state structures provide new insights into Na(V) channel gating and novel avenues to drug development and therapy for a range of debilitating Na(V) channelopathies...
  5. pmc Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel
    Xu Zhang
    State Key Laboratory of Bio membrane and Membrane Biotechnology, Center for Structural Biology, Tsinghua University, Beijing 100084, China
    Nature 486:130-4. 2012
    ..We propose that Na(v)Rh is in an 'inactivated' conformation. Comparison of Na(v)Rh with Na(v)Ab reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels...
  6. ncbi Mechanism of voltage gating in potassium channels
    Morten Ø Jensen
    D E Shaw Research, New York, NY 10036, USA
    Science 336:229-33. 2012
    ..We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data...
  7. ncbi hERG potassium channels and cardiac arrhythmia
    Michael C Sanguinetti
    Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, Utah 84112, USA
    Nature 440:463-9. 2006
    ..Insights gained from the crystal structures of other potassium channels have helped our understanding of the block of hERG channels and the mechanisms of gating...
  8. 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...
  9. pmc Molecular mechanism of ATP binding and ion channel activation in P2X receptors
    Motoyuki Hattori
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 485:207-12. 2012
    ..the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown...
  10. pmc Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel
    Stephen G Brohawn
    Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 335:436-41. 2012
    ..Two diagonally opposed gate-forming inner helices form membrane-interacting structures that may underlie this channel's sensitivity to chemical and mechanical properties of the cell membrane...
  11. 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...
  12. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
    ..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  13. pmc Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2
    Scott B Hansen
    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA
    Nature 477:495-8. 2011
    ....
  14. pmc In search of a consensus model of the resting state of a voltage-sensing domain
    Ernesto Vargas
    Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
    Neuron 72:713-20. 2011
    ..The resulting structural model is in broad agreement with results that originate from various labs using different techniques, indicating the emergence of a consensus for the structural basis of voltage sensing...
  15. pmc Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain
    Georges A Haddad
    Groupe d étude des protéines membranaires, Departement de Physique, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
    J Gen Physiol 137:455-72. 2011
    ..Mode shift is caused by the stabilization of the open state but leads to a conformational change in the voltage sensor...
  16. ncbi Mechanism of calcium gating in small-conductance calcium-activated potassium channels
    X M Xia
    Vollum Institute, Oregon Health Sciences University, Portland 97201, USA
    Nature 395:503-7. 1998
    ..Our data support a model in which calcium gating of SK channels is mediated by binding of calcium to calmodulin and subsequent conformational alterations in the channel protein...
  17. ncbi Hyperpolarization-activated cation channels: from genes to function
    Martin Biel
    Center for Integrated Protein Science CIPS M and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, Munich D 81377, Germany
    Physiol Rev 89:847-85. 2009
    ..Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets...
  18. pmc Structural mechanism of C-type inactivation in K(+) channels
    Luis G Cuello
    Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA
    Nature 466:203-8. 2010
    ..These structures indicate a molecular basis for C-type inactivation in K(+) channels...
  19. ncbi A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel
    M C Sanguinetti
    Eccles Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA
    Cell 81:299-307. 1995
    ..Since block of IKr is a known mechanism for drug-induced cardiac arrhythmias, the finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT...
  20. pmc Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel
    Peng Yuan
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA
    Nature 481:94-7. 2012
    ..These findings present a molecular basis for Ca(2+) activation of K(+) channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension...
  21. ncbi Refined structure of the nicotinic acetylcholine receptor at 4A resolution
    Nigel Unwin
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    J Mol Biol 346:967-89. 2005
    ..Access to the pore on the intracellular side is further influenced by narrow lateral windows, which would be expected to screen out electrostatically ions of the wrong charge and size...
  22. ncbi A model for human ventricular tissue
    K H W J ten Tusscher
    Department of Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands
    Am J Physiol Heart Circ Physiol 286:H1573-89. 2004
    ..We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue...
  23. pmc X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor
    Alexander I Sobolevsky
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 462:745-56. 2009
    ..We exploit the GluA2 structure to develop mechanisms of ion channel activation, desensitization and inhibition by non-competitive antagonists and pore blockers...
  24. 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
    ..This article presents the molecular relationships and physiological functions of these calcium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  25. ncbi X-ray structure of a prokaryotic pentameric ligand-gated ion channel
    Ricarda J C Hilf
    Department of Biochemistry, University of Zurich, Winterthurer Strasse 190, CH 8057 Zurich, Switzerland
    Nature 452:375-9. 2008
    ..3 A resolution. Our study reveals the first structure of a pLGIC at high resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating within the family...
  26. ncbi KATP channels as molecular sensors of cellular metabolism
    Colin G Nichols
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nature 440:470-6. 2006
    ..In parallel, the uncovering of disease-causing mutations of K(ATP) has led to an explanation of the molecular basis of disease and, in turn, to a better understanding of the structural basis of channel function...
  27. pmc Ion channel voltage sensors: structure, function, and pathophysiology
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Neuron 67:915-28. 2010
    ..The emerging structural model for voltage sensor function opens the way to development of a new generation of ion-channel drugs that act on voltage sensors rather than blocking the pore...
  28. pmc Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution
    Peng Yuan
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA
    Science 329:182-6. 2010
    ..The structure suggests that the Ca2+ gating ring, in addition to regulating the pore directly, may also modulate the voltage sensor...
  29. pmc A voltage-gated proton-selective channel lacking the pore domain
    I Scott Ramsey
    Howard Hughes Medical Institute, Department of Cardiology, Children s Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 440:1213-6. 2006
    ..The data presented here identify H(v)1 as a long-sought voltage-gated H+ channel and establish H(v)1 as the founding member of a family of mammalian VSD proteins...
  30. pmc A gating charge transfer center in voltage sensors
    Xiao Tao
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA
    Science 328:67-73. 2010
    ..By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening...
  31. pmc Neural KCNQ (Kv7) channels
    David A Brown
    Department of Pharmacology, University College London, London, UK
    Br J Pharmacol 156:1185-95. 2009
    ..Flupirtine is in use as a central analgesic; retigabine is under clinical trial as a broad-spectrum anticonvulsant and is an effective analgesic in animal models of chronic inflammatory and neuropathic pain...
  32. ncbi Pathways modulating neural KCNQ/M (Kv7) potassium channels
    Patrick Delmas
    Laboratoire de Neurophysiologie Cellulaire, UMR 6150 CNRS, Faculte de Medecine, IFR Jean Roche, Bd Pierre Dramard, 13916 Marseille Cedex 20, France
    Nat Rev Neurosci 6:850-62. 2005
    ..However, until recently, the link between the receptors and the channels has remained elusive. Here, we summarize recent developments that have begun to clarify this link and discuss their implications for physiology and medicine...
  33. ncbi Preassociation of calmodulin with voltage-gated Ca(2+) channels revealed by FRET in single living cells
    M G Erickson
    Department of Biomedical Engineering, Calcium Signals Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 31:973-85. 2001
    ..These results now definitively demonstrate channel-CaM preassociation in resting cells and underscore the potential of three-cube FRET for probing protein-protein interactions...
  34. ncbi Conus venoms: a rich source of novel ion channel-targeted peptides
    Heinrich Terlau
    AG Molekulare und Zelluläre Neuropharmakologie, Max Planck Institut fur experimentelle Medizin, Gottingen, Germany
    Physiol Rev 84:41-68. 2004
    ..This review focuses on the targeting specificity of conotoxins and their differential binding to different states of an ion channel...
  35. pmc Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel
    Yunkun Wu
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9040, USA
    Nature 466:393-7. 2010
    ....
  36. pmc Structural basis for the coupling between activation and inactivation gates in K(+) channels
    Luis G Cuello
    Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA
    Nature 466:272-5. 2010
    ..We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K(+) channels...
  37. ncbi Voltage-gated ion channels and gating modifier toxins
    William A Catterall
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Toxicon 49:124-41. 2007
    ..The voltage-sensor trapping mechanism may be a common mode of action for polypeptide gating modifier toxins acting on all of the voltage-gated ion channels...
  38. pmc Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+) channels
    Seok Yong Lee
    Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA
    PLoS Biol 7:e47. 2009
    ..This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate...
  39. ncbi Contributions of counter-charge in a potassium channel voltage-sensor domain
    Stephan A Pless
    Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    Nat Chem Biol 7:617-23. 2011
    ..Our results suggest that neither Glu293 nor Asp316 engages in electrostatic state-dependent charge-charge interactions with S4, likely because they occupy, and possibly help create, a water-filled vestibule...
  40. pmc Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
    Fredrick Van Goor
    Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 106:18825-30. 2009
    ..These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway...
  41. ncbi Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels
    Martin Tristani-Firouzi
    Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    J Biol Chem 277:18994-9000. 2002
    ..Moreover, our findings suggest that the C-terminal ends of S4 and S6 are in close proximity at hyperpolarized membrane potentials...
  42. pmc A family of potassium channel genes related to eag in Drosophila and mammals
    J W Warmke
    Laboratory of Genetics, University of Wisconsin, Madison 53706
    Proc Natl Acad Sci U S A 91:3438-42. 1994
    ....
  43. pmc Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations
    Yuanyuan Cui
    Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA 95616, USA
    J Gen Physiol 139:273-83. 2012
    ..Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate...
  44. pmc Connexin channel permeability to cytoplasmic molecules
    Andrew L Harris
    Department of Pharmacology and Physiology, New Jersey Medical School of UMDNJ, Newark, NJ 07103, USA
    Prog Biophys Mol Biol 94:120-43. 2007
    ..At this time, the nature of those interactions is unclear. One hopes that with more detailed permeability and structural information, the specific molecular mechanisms of the selectivity can be elucidated...
  45. pmc PIP2 is a necessary cofactor for ion channel function: how and why?
    Byung Chang Suh
    Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195, USA
    Annu Rev Biophys 37:175-95. 2008
    ..This review discusses the dependence of ion channels on phosphoinositides and considers possible mechanisms by which PIP2 and analogues regulate ion channel activity...
  46. 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...
  47. pmc Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor
    Deborah L Capes
    Department of Neuroscience, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 109:2648-53. 2012
    ..Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels...
  48. pmc Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels
    Jing Yao
    Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA
    Proc Natl Acad Sci U S A 108:11109-14. 2011
    ..Our results support that thermal transient receptor potential channels contain modular thermal sensors that confer the unprecedentedly strong temperature dependence to these channels...
  49. ncbi Structural basis for modulation and agonist specificity of HCN pacemaker channels
    William N Zagotta
    Department of Physiology and Biophysics, Howard Hughes Medical Institute, Box 357290, University of Washington School of Medicine, Seattle, Washington 98195 7290, USA
    Nature 425:200-5. 2003
    ..On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism...
  50. ncbi Structure of the connexin 26 gap junction channel at 3.5 A resolution
    Shoji Maeda
    Institute for Protein Research, Osaka University, OLABB, 6 2 3, Furuedai, Suita, Osaka 565 0874, Japan
    Nature 458:597-602. 2009
    ..The structure of the Cx26 gap junction channel also has implications for the gating of the channel by the transjunctional voltage...
  51. ncbi X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation
    Nicolas Bocquet
    Pasteur Institute, G5 Group of Channel Receptor, CNRS URA 2182
    Nature 457:111-4. 2009
    ..These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation...
  52. pmc An intersubunit interaction between S4-S5 linker and S6 is responsible for the slow off-gating component in Shaker K+ channels
    Zarah Batulan
    Département de Physique and Groupe d Etude des Protéines Membranaires, Universite de Montreal, Montreal, Quebec H3C 3J7 Canada
    J Biol Chem 285:14005-19. 2010
    ..Development of this interaction occurs under physiological ion conduction and is correlated with pore opening. We, thus, suggest that the above residues stabilize the channel in the open state...
  53. ncbi Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons
    J C Magee
    Neuroscience Center, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA
    J Neurosci 18:7613-24. 1998
    ..Overall, Ih acts to dampen dendritic excitability, but its largest impact is on the subthreshold range of membrane potentials where the integration of inhibitory and excitatory synaptic inputs takes place...
  54. ncbi Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel
    Ricarda J C Hilf
    Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Nature 457:115-8. 2009
    ..In combination, both structures suggest a novel gating mechanism for pentameric ligand-gated ion channels where channel opening proceeds by a change in the tilt of the pore-forming helices...
  55. pmc Sensing voltage across lipid membranes
    Kenton J Swartz
    Porter Neuroscience Research Center, Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 456:891-7. 2008
    ..Although further structures are needed to understand the conformational changes that occur during voltage sensing, the available data help to frame several key concepts that are fundamental to the mechanism of voltage sensing...
  56. pmc Connexin 43 hemichannels are permeable to ATP
    Jian Kang
    Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA
    J Neurosci 28:4702-11. 2008
    ..Furthermore, a putative Cx43 hemichannel with characteristics identical to the Cx43 hemichannel in C6 cells was identified in the membrane of hippocampal astrocytes in acutely prepared slices...
  57. ncbi HERG, a human inward rectifier in the voltage-gated potassium channel family
    M C Trudeau
    Department of Physiology, University of Wisconsin Medical School, Madison 53706, USA
    Science 269:92-5. 1995
    ..Because mutations in HERG cause a form of long-QT syndrome, these properties of HERG channel function may be critical to the maintenance of normal cardiac rhythmicity...
  58. ncbi Molecular diversity of K+ channels
    W A Coetzee
    Department of Physiology, New York University School of Medicine, New York 10016, USA
    Ann N Y Acad Sci 868:233-85. 1999
    ....
  59. ncbi The inward rectification mechanism of the HERG cardiac potassium channel
    P L Smith
    Department of Neurobiology, Harvard Medical School, Boston, MA 02114 2698, USA
    Nature 379:833-6. 1996
    ..The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias...
  60. ncbi Global twisting motion of single molecular KcsA potassium channel upon gating
    Hirofumi Shimizu
    CREST Sasaki team, Japan Science and Technology Corporation, Tachikawa, Tokyo, 190 0012, Japan
    Cell 132:67-78. 2008
    ..This coupling suggests a mechanical interplay between the transmembrane and cytoplasmic domains...
  61. ncbi Crystal structure of the human two-pore domain potassium channel K2P1
    Alexandria N Miller
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Science 335:432-6. 2012
    ..An interfacial helix appears structurally poised to affect gating. The structure lays a foundation to further investigate how K2P channels are regulated by diverse stimuli...
  62. ncbi Binding, activation and modulation of Cys-loop receptors
    Paul S Miller
    Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
    Trends Pharmacol Sci 31:161-74. 2010
    ..This review considers our current understanding about the processes of agonist binding, receptor activation and channel opening, as well as allosteric modulation of the Cys-loop receptor family...
  63. ncbi X-ray structure of the mammalian GIRK2-βγ G-protein complex
    Matthew R Whorton
    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 498:190-7. 2013
    ..The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na(+) ions participate in multi-ligand regulation of GIRK channels...
  64. pmc Electrophysiology and beyond: multiple roles of Na+ channel β subunits in development and disease
    Gustavo A Patino
    Department of Pharmacology and Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States
    Neurosci Lett 486:53-9. 2010
    ..In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system...
  65. 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...
  66. ncbi HCN channels: structure, cellular regulation and physiological function
    C Wahl-Schott
    Center for Integrated Protein Science CIPSM and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, 81377 Munchen, Germany
    Cell Mol Life Sci 66:470-94. 2009
    ..In this review we give an overview on structure, function and regulation of HCN channels. Particular emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity...
  67. pmc BK potassium channel modulation by leucine-rich repeat-containing proteins
    Jiusheng Yan
    Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 109:7917-22. 2012
    ....
  68. pmc Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function
    Adrian W R Serohijos
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 105:3256-61. 2008
    ....
  69. pmc Mechanistic insight into human ether-à-go-go-related gene (hERG) K+ channel deactivation gating from the solution structure of the EAG domain
    Frederick W Muskett
    Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom
    J Biol Chem 286:6184-91. 2011
    ..We propose a model in which NT1-26 obstructs gating motions of the cyclic nucleotide binding domain to allosterically stabilize the open conformation of the pore...
  70. 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...
  71. pmc Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel
    Arthur Beyder
    Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    J Physiol 588:4969-85. 2010
    ..These data suggest that mechanical activation of Na(v)1.5 results in dose-dependent voltage dependence shifts of activation and inactivation due to mechanical modulation of the voltage sensors...
  72. pmc Mechanism of activation gating in the full-length KcsA K+ channel
    Serdar Uysal
    Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 108:11896-9. 2011
    ..We suggest that by limiting the extent to which the inner gate can open, the cytoplasmic domain also modulates the level of inactivation occurring at the selectivity filter...
  73. pmc Properties of deactivation gating currents in Shaker channels
    Jérôme J Lacroix
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA
    Biophys J 100:L28-30. 2011
    ..We propose a new (to our knowledge) kinetic model that accounts for these observations...
  74. pmc Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel
    M E Gellens
    Department of Medicine, University of Pennsylvania, Philadelphia 19104
    Proc Natl Acad Sci U S A 89:554-8. 1992
    ..7 microM). hH1 is also resistant to mu-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner...
  75. pmc Structural basis for gating charge movement in the voltage sensor of a sodium channel
    Vladimir Yarov-Yarovoy
    Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:E93-102. 2012
    ..We confirmed the validity of these structural models by comparing with a high-resolution structure of a NaChBac homolog and showing predicted molecular interactions of hydrophobic residues in the S4 segment in disulfide-locking studies...
  76. pmc Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor
    Jérôme J Lacroix
    Department of Biochemistry and Molecular Biology, University of Chicago, Gordon Center for Integrative Sciences W244, 929 East 57th Street, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 108:6444-9. 2011
    ..Our results suggest that F(290) controls the transfer of R(371), the fourth gating charge, during gating while not affecting the movement of the other three gating arginines...
  77. pmc The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation
    Chai Ann Ng
    Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
    PLoS ONE 6:e16191. 2011
    ....
  78. pmc Principles of conduction and hydrophobic gating in K+ channels
    Morten Ø Jensen
    DE Shaw Research, New York, NY 10036, USA
    Proc Natl Acad Sci U S A 107:5833-8. 2010
    ....
  79. ncbi Multiple regulatory sites in large-conductance calcium-activated potassium channels
    Xiao Ming Xia
    Department of Anesthesiology, Washington University School of Medicine, Box 8054, St Louis, Missouri 63110, USA
    Nature 418:880-4. 2002
    ..This allows BK channels to serve a variety of physiological roles contingent on the Ca(2+) concentration to which the channels are exposed...
  80. 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
    ..Recent status of the pharmacology and molecular identification of CaCCs is evaluated...
  81. ncbi Subunit arrangement and function in NMDA receptors
    Hiroyasu Furukawa
    Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, New York 10032, USA
    Nature 438:185-92. 2005
    ....
  82. ncbi K+ channels and the microglial respiratory burst
    R Khanna
    Division of Cellular and Molecular Biology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada
    Am J Physiol Cell Physiol 280:C796-806. 2001
    ..The respiratory burst was markedly inhibited by blockers of SK2 (apamin) and SK4 channels (clotrimazole and charybdotoxin), and to a lesser extent, by the potent Kv1.3 blocker agitoxin-2...
  83. ncbi Blocker protection in the pore of a voltage-gated K+ channel and its structural implications
    D del Camino
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:321-5. 2000
    ..This bend would occur at a Pro-X-Pro sequence that is highly conserved in Kv channels, near the site of activation gating...
  84. pmc Integrated allosteric model of voltage gating of HCN channels
    C Altomare
    Dipartimento di Fisiologia e Biochimica Generali, Via Celoria 26, , Via Celoria 16, 20133 Milano, Italy
    J Gen Physiol 117:519-32. 2001
    ..HCN voltage gating thus involves two processes: voltage sensor gating and allosteric opening/closing...
  85. pmc Overview of the voltage-gated sodium channel family
    Frank H Yu
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Genome Biol 4:207. 2003
    ..The different sodium channels have remarkably similar functional properties, but small changes in sodium-channel function are biologically relevant, as underscored by mutations that cause several human diseases of hyperexcitability...
  86. pmc The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels
    Walter Marcotti
    School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
    J Physiol 567:505-21. 2005
    ....
  87. ncbi Molecular basis of mechanotransduction in living cells
    O P Hamill
    Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Physiol Rev 81:685-740. 2001
    ..e., tethers) may transmit mechanical forces to the process (e.g., hair cell MG channels, MS intracellular Ca(2+) release, and transmitter release) without increasing tension in the lipid bilayer...
  88. pmc Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome
    Helmuth A Sánchez
    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Gen Physiol 136:47-62. 2010
    ..A40V produces leaky hemichannels, whereas G45E provides a route for excessive entry of Ca(2+). These aberrant properties, alone or in combination, can severely compromise cell integrity and lead to increased cell death...
  89. ncbi The principle of gating charge movement in a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:42-8. 2003
    ..Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore...
  90. pmc Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide
    S Chen
    Department of Pharmacology, ColumbiaUniversity, New York, New York 10032, USA
    J Gen Physiol 117:491-504. 2001
    ..Finally, differences in Ih channel properties recorded in cell-free patches versus intact oocytes are shown to be due, in part, to modulation of Ih by basal levels of cAMP in intact cells...
  91. pmc BK channel activation: structural and functional insights
    Urvi S Lee
    Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130, USA
    Trends Neurosci 33:415-23. 2010
    ..This review discusses these latest findings and an emerging new understanding about BK channel gating and implications for diseases such as epilepsy, in which mutations in BK channel genes have been associated...
  92. 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...
  93. pmc Interactions between lipids and voltage sensor paddles detected with tarantula toxins
    Mirela Milescu
    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    Nat Struct Mol Biol 16:1080-5. 2009
    ..Our results suggest that lipids bind to voltage-sensing domains and demonstrate that the pharmacological sensitivities of voltage-activated ion channels are influenced by the surrounding lipid membrane...
  94. pmc Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain
    Mamoru Takeda
    Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1 9 20 Fujimi cho, Chiyoda ku, Tokyo, Japan
    Mol Pain 7:5. 2011
    ..We also discuss the potential of Kv channel openers as therapeutic agents for trigeminal neuropathic/inflammatory pain, such as mechanical allodynia...
  95. ncbi Molecular identification of a hyperpolarization-activated channel in sea urchin sperm
    R Gauss
    Institut für Biologische Informationsverarbeitung, Forschungszentrum Julich, Germany
    Nature 393:583-7. 1998
    ..Because of their sequence and functional properties, Ih channels form a class of their own within the superfamily of voltage-gated and cyclic-nucleotide-gated channels...
  96. ncbi Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel
    David T Wang
    Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, New South Wales, Australia
    Nat Struct Mol Biol 18:35-41. 2011
    ..1 K(+) channel...
  97. pmc TRIP8b splice variants form a family of auxiliary subunits that regulate gating and trafficking of HCN channels in the brain
    Bina Santoro
    Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA
    Neuron 62:802-13. 2009
    ..TRIP8b thus functions as an auxiliary subunit that provides a mechanism for the dynamic regulation of HCN1 channel expression and function...
  98. ncbi Cytosolic pH regulates root water transport during anoxic stress through gating of aquaporins
    Colette Tournaire-Roux
    Biochimie et Physiologie Moleculaire des Plantes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5004, Institut National de la Recherche Agronomique, Université Montpellier 2 et Ecole Nationale d Agronomie, Montpellier, France
    Nature 425:393-7. 2003
    ..More generally, our work opens new routes to explore pH-dependent cell signalling processes leading to regulation of water transport in plant tissues or in animal epithelia...
  99. pmc Atomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues
    Pierre Jean Corringer
    Pasteur Institute, G5 Group of Channel Receptor, CNRS URA 2182, 75015 Paris, France
    J Physiol 588:565-72. 2010
    ..This mechanism couples opening-closing motions of the channel with a global reorganization of the protein, including the subunit interface that holds the neurotransmitter binding sites in eukaryotic pLGICs...
  100. pmc Number and locations of agonist binding sites required to activate homomeric Cys-loop receptors
    Diego Rayes
    Instituto de Investigaciones Bioquimicas, Universidad Nacional del Sur Consejo Nacional de Investigaciones Científicas y Técnicas, 8000 Bahia Blanca, Argentina
    J Neurosci 29:6022-32. 2009
    ..The overall results provide a framework for defining mechanisms of activation and drug modulation for homo-pentameric Cys-loop receptors...
  101. pmc Pore region of TRPV3 ion channel is specifically required for heat activation
    JORG GRANDL
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Neurosci 11:1007-13. 2008
    ..Although molecular mechanisms of ion channel gating by chemical and voltage stimuli are understood in principal, the mechanisms of temperature activation remain ..

Research Grants63

  1. General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets
    Stuart A Forman; Fiscal Year: 2013
    ..M1 and M3 domains on adjacent subunits form amphiphilic anesthetic-binding pockets that change shape during ion channel gating. Hetero-pentameric synaptic GABAA receptors containing 13, 21, and 22 subunits form four distinct types of ..
  2. Mechanisms of Calcium-Calmodulin Mediated Ion Channel Gating
    Richard Aldrich; Fiscal Year: 2013
    ..Our studies will contribute to understanding the function of an important class of ion channel, and general principles of ion channel gating, calcium/calmodulin regulatory mechanisms, and allosteric control of protein function.
  3. MOLECULAR CLONING OF EPITHELIAL K CHANNELS
    Henry Sackin; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: The proposed project would characterize the underlying molecular basis for ion channel gating (opening &closing) in the renal inward rectifier (ROMK) family of potassium (K) channels...
  4. High Resolution Structural Dyanmics of K Channels
    EDUARDO A PEROZO; Fiscal Year: 2013
    ..to our understanding of biologically important events such as electrical signaling, signal transduction and ion channel gating. PUBLIC HEALTH RELEVANCE: Understanding of K+ channel structure and function relates directly to health and ..
  5. Gating Mechanisms of the Prokaryotic Calcium Activated Potassium channel MthK
    DAVID JOHN POSSON; Fiscal Year: 2010
    DESCRIPTION (provided by candidate): Ion channel gating, the ability of channels to switch between an open conducting state and a closed non- conducting state, is the most fundamental mechanistic feature of channels throughout physiology...
  6. Structural Mechanisms of Gating in KATP Channels
    Jeremy D Bushman; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): The goal of this research is to establish a general mechanism of ion channel gating for potassium channels in pursuit of a functional model for use in therapeutic development...
  7. CA2+DEPENDENT K+CHANNELS: ALLOSTERIC GATING
    Jianmin Cui; Fiscal Year: 2013
    ..The dissection of the molecular events during BK channel gating in this study will help identify specific targets for the development of therapeutics in addition to providing insights into the principles of ion channel gating.
  8. Temperature-Dependent Gating of Vanilloid Receptors
    Feng Qin; Fiscal Year: 2013
    ..temperature-dependent gating, using approaches that have proven successful for understanding other types of ion channel gating. Aim 1 focuses on the physical basis of thermal sensors...
  9. Thermodynamics and energetics of voltage-gated ion channels
    Baron Chanda; Fiscal Year: 2013
    ..we would have made significant headway in testing molecular theories that may underlie the temperature-dependence of ion channel gating, developed a new model system and refined our knowledge of the role of water in ion channel gating.
  10. Allosteric Regulation of Ion Channel Gating
    Christopher J Lingle; Fiscal Year: 2013
    ....
  11. Voltage-Dependent Ion Channel Gating
    Roderick MacKinnon; Fiscal Year: 2013
    ..An in-depth understanding of the atomic structure and mechanisms of voltage- dependent ion channels holds promise for new approaches in the future to treat diseases such as epilepsy and cardiac arrhythmia. ..
  12. Molecular Mechanisms of Hv1 Voltage-Gated Proton Channel Function
    IAN SCOTT RAMSEY; Fiscal Year: 2013
    ..Hv1 function in detail will provide fundamental insights into the mechanisms of proton transport and ion channel gating, and ultimately facilitate the development of therapies to cure diseases that result from Hv1 dysfunction.
  13. Alcohol actions on NMDA receptor gating domains
    ROBERT WILLIAM PEOPLES; Fiscal Year: 2013
    ..Alcohol inhibits NMDA receptors by influencing ion channel gating (1;2), and results of recent studies from this and other laboratories point to sites in the membrane-..
  14. Neurotoxin interactions with ligand-gated ion channels
    GLENN DILLON; Fiscal Year: 2004
    ..will provide fundamental information about the characteristics of channel-lining amino acids that influence ion channel gating and permeation...
  15. CHEMOSENSORY MECHANISMS IN CULTURED CAROTID BODY CELLS
    Colin Nurse; Fiscal Year: 1991
    ..Finally, the possible role of Ca2+ and H+ ions in chemosensory transduction and the involvement of various neurotransmitters will be investigated in these cultures...
  16. Ca2+-gating of SK Channels: Atomic Structure and Function
    John Adelman; Fiscal Year: 2005
    ..complex exists as a monomer of one CaMBD molecule and one CaM molecule, we have presented a novel model for ion channel gating in which a Ca2+-dependent dimer-of-dimers mediates chemomechanical gating...
  17. CNG Channel Gating Movements Monitored via Fluorescene Quenching
    MICHAEL PULJUNG; Fiscal Year: 2009
    ..Therefore, not only will the proposed studies be informative with respect to ion channel gating mechanisms, but they will also provide insight into the movements of structurally-related molecules, ..
  18. Mechanisms and Kinetics of Gating in K Channels
    Decha Enkvetchakul; Fiscal Year: 2005
    ..2), and potassium secretion in the kidney (Kir1.1). Mutations that alter ion channel gating can cause diseases, e.g., Bartters syndrome, and diabetes...
  19. VOLTAGE-GATED PROTON CHANNELS IN HUMAN NEUTROPHILS
    THOMAS DECOURSEY; Fiscal Year: 2008
    ..5) We will identify the proton channel molecule and gene. ..
  20. MOLECULAR MECHANISMS OF GLUTAMATE RECEPTOR CHANNELS
    Anthony Auerbach; Fiscal Year: 2007
    ..Accordingly, we will better understand the mechanisms by which transmitters, drugs, and other ligands shape the cellular responses of neurons that express these important receptor-channel proteins. ..
  21. VOLTAGE-GATED PROTON CHANNELS IN ALVEOLAR EPITHELIUM
    THOMAS DECOURSEY; Fiscal Year: 2003
    ..Demonstration that H+ current fluctuations result from stochastic gating of H+ channels will provide strong evidence that the molecule is an ion channel rather than a carrier. ..
  22. TRAINING IN MOLECULAR NEUROBIOLOGY
    William Catterall; Fiscal Year: 2008
    ..The training program will integrate the substantial expertise of this group of faculty in a coordinated pre-doctoral and post-doctoral training effort. ..
  23. MOLECULAR CLONING OF EPITHELIAL K CHANNELS
    Henry Sackin; Fiscal Year: 2008
    ..A thorough characterization of their gating is essential for understanding the molecular basis of a variety of channelopathies. ..
  24. Actions of Ethanol on Ligand-Gated Ion Channels
    Gustav Akk; Fiscal Year: 2006
    ..The results from the experiments will be used to examine the mechanism and structural requirements in the ethanol-mediated modulation of the GABAA receptor function. ..
  25. Cellular Physiology of Podocytes
    Stuart E Dryer; Fiscal Year: 2010
    ..Practically nothing is currently known about the effects of insulin on podocytes, which limits what we can know about diabetic nephropathy, especially in its earliest stages. ..
  26. Neural Calcium Channels-Regulation and Function
    Diane Lipscombe; Fiscal Year: 2009
    ..2. This novel interaction is likely to mediate coupling of the CaV2.2 channel to the synaptic release machinery (aim 3). ..
  27. INSECTICIDE ACTIONS ON GABA-A RECEPTORS
    Gustav Akk; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  28. CIRCADIAN REGULATION OF VERTEBRATE PHOTORECEPTORS
    STUART DRYER; Fiscal Year: 2005
    ..abstract_text> ..
  29. DEVELOPMENT OF IONIC CHANNELS
    STUART DRYER; Fiscal Year: 2005
    ..Neurotrophic factors are potential therapeutic agents for neurodegeneration. This research will provide additional information on neurotrophic factor actions and interactions, especially with respect to posttranslational effects. ..
  30. Circadian Regulation of Olfaction
    STUART DRYER; Fiscal Year: 2004
    ..abstract_text> ..
  31. Molecular Physiology of Neuromusclar Diseases
    Stephen Cannon; Fiscal Year: 2007
    ..abstract_text> ..
  32. PHARMACOLOGY OF CARDIAC SODIUM CHANNEL MODIFIERS
    Michael Sheets; Fiscal Year: 2008
    ..The results of these studies should improve our overall understanding of the molecular mechanisms of anti-arrhythmic drugs modification of cardiac Na channels. [unreadable] [unreadable]..
  33. Mechanisms of Nociceptive Neuronal Plasticity
    ARMEN AKOPIAN; Fiscal Year: 2004
    ..abstract_text> ..
  34. ELECTROPHYSIOLOGY OF NUCLEAR MEMBRANE INSP3 RECEPTOR
    J Kevin Foskett; Fiscal Year: 2010
    ..The results of these studies should provide important insights into the molecular mechanisms that regulate apoptosis, and into the development of novel targets for therapeutic interventions in human diseases. ..
  35. STRUCTURE-FUNCTION OF CONNEXIN PORES
    Andrew Harris; Fiscal Year: 2009
    ..In the present proposal, this analysis will be applied to Cx32 and Cx26, defects in which cause X-linked Charcot-Marie-Tooth disease neuropathy and sensorineural deafness, respectively. ..
  36. Properties of Ion Channels that Control Secretion
    JOHN ENYEART; Fiscal Year: 2008
    ..abstract_text> ..
  37. Dendritic Processing in the Olfactory Bulb
    Jason Christie; Fiscal Year: 2003
    ..The specific aims are: (1) to determine the function of autoexcitation in mitral cell processing and (2) to determine how dendritic compartmentalization effects mitral cell processing. ..
  38. Molecular Mechanisms of Na Channel Slow Inactivation
    ARIE STRUYK; Fiscal Year: 2005
    ..abstract_text> ..
  39. Mechanisms of CIC Chloride Transport Proteins
    Merritt Maduke; Fiscal Year: 2009
    ..Together, these studies will offer new insights into the functional relationships between channels and transporters. ..
  40. INTERACTIONS OF TRPV1 AND TRPA1 AND INFLAMMATORY PAIN
    Armen N Akopian; Fiscal Year: 2010
    ..abstract_text> ..
  41. Drug therapy targeted to the voltage-gated sodium channel
    Michael F Sheets; Fiscal Year: 2010
    ..In pursuance of this hypothesis we will determine the residues at the bundle crossing by crosslinking Cys substitutions between S6 segments. ..
  42. SNTS--DEVELOPMENTAL FUNCTIONS AND RECEPTOR INTERACTIONS
    Mitchell Goldfarb; Fiscal Year: 2002
    ..To this end, chimeric SNT-IRS as well as insulin receptor-Trk hybrids will be produced to determine if they can turn insulin response to that of neurotrophins or FGFs. ..
  43. MODULATION OF CONNEXIN CHANNEL ACTIVITY
    Andrew Harris; Fiscal Year: 2002
    ..Such defects will result in abnormal (i.e., greater or lesser) intercellular signaling molecules. The proposed studies address how this may occur. ..
  44. STRUCTURAL BASES OF T-TYPE CALCIUM CHANNEL FUNCTION
    DOROTHY HANCK; Fiscal Year: 2003
    ..These experiments will use techniques of electrophysiology, mutagenesis and molecular modeling. ..
  45. PROPERTIES OF CONNEXIN CHANNELS THAT CAUSE DEAFNESS
    Andrew Harris; Fiscal Year: 2006
    ..The information obtained will be informative regarding connexin channel function in other contexts, and will lead to insights about mechanisms of selectivity among cytoplasmic permeants. ..
  46. Cardiac Channels: Targets of Drugs that Affect Kinetics
    Dorothy A Hanck; Fiscal Year: 2010
    ..Our strategy combines mutagenesis, whole cell, single channel, and gating current electrophysiology, and molecular modeling. ..
  47. CALMODULIN KINASE II AND EARLY AFTERDEPOLARIZATIONS
    Mark Anderson; Fiscal Year: 2007
    ..unreadable] [unreadable] Understanding these molecular mechanisms for Ca2+/CaM-dependent ICa facilitation will likely be necessary to develop improved therapies for TdP. [unreadable] [unreadable]..
  48. PERMEABILITY MEDIATED BY CONNEXIN CHANNELS
    Andrew Harris; Fiscal Year: 2007
    ..The information obtained will inform cellular and physiological studies of intercellular communication in disease and development. ..
  49. NEURONAL FUNCTIONS OF FHFS
    Mitchell Goldfarb; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  50. Development of isoform specific sensory neuronal sodium channel blockers
    THEODORE CUMMINS; Fiscal Year: 2008
    ..The long-term goal of this research is to develop sodium channel blockers that are useful as novel therapeutics for the treatment of neurological disorders of hyperexcitability such as chronic pain. [unreadable] [unreadable] [unreadable]..
  51. STRUCTURE-FUNCTION OF THE CARDIAC SODIUM CHANNEL
    DOROTHY HANCK; Fiscal Year: 2008
    ..abstract_text> ..
  52. Mechanisms of Neurotransmitter-gated Ion Channels
    Claudio Grosman; Fiscal Year: 2007
    ..abstract_text> ..
  53. Biophysics of CNS Connexins
    VYTAUTAS VERSELIS; Fiscal Year: 2006
    ..abstract_text> ..
  54. Structural Dynamics of Mechanosensitive Channels
    Eduardo Perozo; Fiscal Year: 2008
    ..This proposal opens up a new experimental avenue that will contribute to the understanding of biologically important events such as ion channel gating, nociception and signal transduction.
  55. Midwest Center for Membrane Protein Structural Dynamics
    Eduardo Perozo; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  56. Stoichiometry and modular retrieval of ENaC
    James Stockand; Fiscal Year: 2009
    ..This research will provide critical insight about the molecualr architecture of ENaC and regulation of this important channel. ..
  57. Using Nanotechnology to Rescue Visual Loss in A Model of Human Blinding Disorder
    Xi Qin Ding; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  58. Signaling Pathways in Salivary Gland Fluid Secretion
    Trevor Shuttleworth; Fiscal Year: 2009
    ..abstract_text> ..
  59. Volatile Anesthesia and the GABAA Receptor Gamma Subunit
    Stuart Forman; Fiscal Year: 2009
    ..abstract_text> ..
  60. Epithelial Na channel (ENaC) polymorphisms in hyptertention
    James Stockand; Fiscal Year: 2007
    ..Preliminary results support the feasibility of this investigation and suggest that this line of inquiry will yield significant and novel findings. [unreadable] [unreadable]..
  61. Confocal Equipment for Biomedical and Nanomedicine Research
    Tzyh Chang Hwang; Fiscal Year: 2006
    ..and nanotechnology approaches to central questions in membrane physiology such as exocytosis/ endocytosis, ion channel gating and receptor- mediated signal transduction...
  62. Permeability of heteromeric heart gap junction channels
    Alonso Moreno; Fiscal Year: 2007
    ..abstract_text> ..