inwardly rectifying potassium channels

Summary

Summary: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.

Top Publications

  1. 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
  2. ncbi Inwardly rectifying potassium channels: their structure, function, and physiological roles
    Hiroshi Hibino
    Department of Pharmacology, Graduate School of Medicine and The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka 565 0871, Japan
    Physiol Rev 90:291-366. 2010
  3. ncbi Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
  4. ncbi Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations
    Ewan R Pearson
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 355:467-77. 2006
  5. ncbi Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
    S J Tucker
    University Laboratory of Physiology, Oxford, UK
    Nature 387:179-83. 1997
  6. pmc Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice
    Masashi Suzuki
    Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan
    J Clin Invest 109:509-16. 2002
  7. ncbi Adenosine diphosphate as an intracellular regulator of insulin secretion
    C G Nichols
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Science 272:1785-7. 1996
  8. ncbi Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 268:423-6. 1995
  9. ncbi Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood
    Sarah E Flanagan
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 56:1930-7. 2007
  10. ncbi A potassium channel-linked mechanism of glial cell swelling in the postischemic retina
    Thomas Pannicke
    Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany
    Mol Cell Neurosci 26:493-502. 2004

Detail Information

Publications355 found, 100 shown here

  1. 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...
  2. ncbi Inwardly rectifying potassium channels: their structure, function, and physiological roles
    Hiroshi Hibino
    Department of Pharmacology, Graduate School of Medicine and The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka 565 0871, Japan
    Physiol Rev 90:291-366. 2010
    ..The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family...
  3. ncbi Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
    ..2 subunit of this channel (KCNJ11) cause neonatal diabetes...
  4. ncbi Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations
    Ewan R Pearson
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 355:467-77. 2006
    ..Diabetes results from impaired insulin secretion caused by a failure of the beta-cell K(ATP) channel to close in response to increased intracellular ATP. Sulfonylureas close the K(ATP) channel by an ATP-independent route...
  5. ncbi Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
    S J Tucker
    University Laboratory of Physiology, Oxford, UK
    Nature 387:179-83. 1997
    ..We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP...
  6. pmc Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice
    Masashi Suzuki
    Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan
    J Clin Invest 109:509-16. 2002
    ..The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcK(ATP) channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals...
  7. ncbi Adenosine diphosphate as an intracellular regulator of insulin secretion
    C G Nichols
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Science 272:1785-7. 1996
    ..Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion...
  8. ncbi Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 268:423-6. 1995
    ..The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release...
  9. ncbi Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood
    Sarah E Flanagan
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 56:1930-7. 2007
    ..Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes...
  10. ncbi A potassium channel-linked mechanism of glial cell swelling in the postischemic retina
    Thomas Pannicke
    Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany
    Mol Cell Neurosci 26:493-502. 2004
    ..Inhibition of these water fluxes may be beneficial to prevent ischemia-evoked glial cell swelling...
  11. ncbi Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy
    P M Thomas
    Department of Medical Specialties, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Science 268:426-9. 1995
    ..Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene...
  12. ncbi Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose
    Chiyo Shiota
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 277:37176-83. 2002
    ....
  13. ncbi Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy
    Andrew T Hattersley
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    Diabetes 54:2503-13. 2005
    ..In conclusion, the finding that Kir6.2 mutations can cause neonatal diabetes has enabled a new therapeutic approach and shed new light on the structure and function of the Kir6.2 subunit of the K(ATP) channel...
  14. ncbi Role of ER export signals in controlling surface potassium channel numbers
    D Ma
    Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0725, USA
    Science 291:316-9. 2001
    ..Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals...
  15. ncbi Ion conduction pore is conserved among potassium channels
    Z Lu
    Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
    Nature 413:809-13. 2001
    ..The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels...
  16. ncbi Overexpression of the G-protein inwardly rectifying potassium channel 1 (GIRK1) in primary breast carcinomas correlates with axillary lymph node metastasis
    B K Stringer
    Department of Pathology, Faulkner Hospital, Boston, Massachusetts 02130, USA
    Cancer Res 61:582-8. 2001
    ..0029), and overexpression was greatest in tumors with more than one positive lymph node. These results indicate that GIRK1 may be useful as a biomarker for lymph node metastasis and possibly a pharmaceutical target...
  17. ncbi Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure
    K Yamada
    Department of Physiology, Akita University School of Medicine, Hondo, Akita 010 8543, Japan
    Science 292:1543-6. 2001
    ..K(ATP) channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures...
  18. ncbi Assaying phosphatidylinositol bisphosphate regulation of potassium channels
    Tibor Rohacs
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Methods Enzymol 345:71-92. 2002
  19. ncbi K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels
    Christina Schwanstecher
    Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, Germany
    Diabetes 51:875-9. 2002
    ..2 in both alleles) genotype, we propose a model in which enhanced susceptibility to type 2 diabetes is associated with evolutionary advantage of the E/K state...
  20. pmc Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line
    Keiko Ishihara
    Department of Physiology, Saga Medical School, 5 1 1 Nabeshima, Saga 849 8501, Japan
    J Physiol 556:61-78. 2004
    ..Polyamines may regulate the amplitude of the outward I(K1), not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block...
  21. ncbi Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1
    E A Nagelhus
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders and Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, POB 1105 Blindern, N 0317 Oslo, Norway
    Neuroscience 129:905-13. 2004
    ..We conclude that AQP4-mediated water flux represents an integral element of brain volume and ion homeostasis...
  22. ncbi Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels
    Eldo V Kuzhikandathil
    Department of Cell and Molecular Physiology and the Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7545, USA
    Mol Pharmacol 62:119-26. 2002
    ..0 family of inwardly rectifying potassium channels, as well as various endogenous cationic currents present in AtT-20 cells, are not affected...
  23. ncbi Activity-dependent homeostatic specification of transmitter expression in embryonic neurons
    Laura N Borodinsky
    Neurobiology Section, Division of Biological Sciences and Center for Molecular Genetics, UCSD, La Jolla, California 92093 0357, USA
    Nature 429:523-30. 2004
    ..The results identify a new role of patterned activity in development of the central nervous system...
  24. pmc A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits
    Y Cui
    Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, United Kingdom
    Proc Natl Acad Sci U S A 98:729-34. 2001
    ..2 or Kir 6.1 expressed with SUR2B. In conclusion, Kir 6.1 and Kir 6.2 readily coassemble to produce functional channels, and such phenomena may contribute to the diversity of nucleotide-regulated potassium currents seen in native tissues...
  25. ncbi Abnormal heart rate regulation in GIRK4 knockout mice
    K Wickman
    Department of Cardiology, Harvard Medical School, Children s Hospital, Boston, Massachusetts 02115, USA
    Neuron 20:103-14. 1998
    ..Interestingly, noncholinergic systems also appear to modulate heart activity through I(KACh). Thus, I(KACh) is critical for effective heart rate regulation in mice...
  26. pmc Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant
    Satsuki Yamada
    Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    J Physiol 577:1053-65. 2006
    ..Thus, K(ATP) channels appear mandatory in acute and chronic cardiac adaptation to imposed haemodynamic load, protecting against congestive heart failure and death...
  27. ncbi A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene
    Silvia G Priori
    Molecular Cardiology, IRCCS Fondazione Maugeri, Pavia, Italy
    Circ Res 96:800-7. 2005
    ....
  28. pmc Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina
    P Kofuji
    Departments of Neuroscience and Physiology, University of Minnesota, Minneapolis 55455, USA
    J Neurosci 20:5733-40. 2000
    ..The highly regulated localization and the functional properties of Kir4.1 in Müller cells suggest the involvement of this channel in the regulation of extracellular K(+) in the mouse retina...
  29. ncbi Toward understanding the assembly and structure of KATP channels
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA
    Physiol Rev 78:227-45. 1998
    ..The availability of cloned KATP channel genes opens the way for characterization of this family of ion channels and identification of additional genetic defects...
  30. ncbi Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations
    Meena Rafiq
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes Care 31:204-9. 2008
    ..2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations...
  31. ncbi Neuroprotection by KATP channels
    Katsuya Yamada
    Department of Physiology, Akita University School of Medicine, Japan
    J Mol Cell Cardiol 38:945-9. 2005
    ..The ATP-sensitive potassium channels in the reticulata neurons may be involved in the protection mechanism against energy-consuming generalized seizure by earlier response to hypoxia than those in other, less active neuron types...
  32. pmc Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations
    Sara E Pinney
    Division of Endocrinology Diabetes, The Children s Hospital of Philadelphia, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 118:2877-86. 2008
    ....
  33. ncbi Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart
    Dzwokai Ma
    Howard Hughes Medical Institute, University of California, San Francisco 94143, USA
    Neuron 33:715-29. 2002
    G protein-activated inwardly rectifying potassium channels (Kir3, GIRK) provide an important mechanism for neurotransmitter regulation of membrane excitability...
  34. ncbi The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins
    G Krapivinsky
    Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905
    Nature 374:135-41. 1995
    ..It is now shown that IKACh is a heteromultimer of two distinct inwardly rectifying K(+)-channel subunits, GIRK1 and a newly cloned member of the family, CIR...
  35. ncbi Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the
    A S Slingerland
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK
    Diabetologia 49:2559-63. 2006
    ..The aim of this study was to investigate the long-term outcome and impact on neurological features of sulfonylurea treatment...
  36. pmc H bonding at the helix-bundle crossing controls gating in Kir potassium channels
    Markus Rapedius
    Institute of Physiology II, Friedrich Schiller University, D 07743 Jena, Germany
    Neuron 55:602-14. 2007
    ....
  37. ncbi Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers
    Juraj Stanik
    DIABGENE and Diabetes Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, SK 833 06 Bratislava, Slovak Republic
    J Clin Endocrinol Metab 92:1276-82. 2007
    ..Thus, the aim of this study was to identify the incidence of PNDM in Slovakia and to switch patients to sulfonylurea (SU) where applicable...
  38. ncbi KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential
    Daniel C Marcus
    Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506 5802, USA
    Am J Physiol Cell Physiol 282:C403-7. 2002
    ..KCNJ10 is also a limiting pathway for K(+) secretion...
  39. ncbi Hypothalamic K(ATP) channels control hepatic glucose production
    Alessandro Pocai
    Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nature 434:1026-31. 2005
    ..These findings suggest that activation of hypothalamic K(ATP) channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycaemia...
  40. pmc Diagnosis and treatment of neonatal diabetes: a United States experience
    Julie Støy
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Pediatr Diabetes 9:450-9. 2008
    ..The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age...
  41. pmc The molecular basis of the specificity of action of K(ATP) channel openers
    C Moreau
    CEA, DBMS, Biophysique Moléculaire et Cellulaire UMR CNRS UJF CEA 5090, 17 rue des Martyrs, 38054 Grenoble, France
    EMBO J 19:6644-51. 2000
    ..This first glimpse of the site of action of pharmacological openers should permit rapid progress towards understanding the structural determinants of their affinity and specificity...
  42. ncbi SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population
    Yukiko Sakamoto
    Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3 18 15, Kuramoto Cho, Tokushima City, Tokushima 770 8503, Japan
    J Hum Genet 52:781-93. 2007
    ..8% Japanese), confirmed the significant role of the KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the KCNJ11 E23K genotype is independently associated with higher blood-pressure levels...
  43. ncbi A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K(+) channels
    C Stockklausner
    Department of Physiology II, University of Tubingen, Ob dem Himmelreich 7, 72074, Tubingen, Germany
    FEBS Lett 493:129-33. 2001
    ..This motif is found to be both necessary and sufficient for efficient export from the ER that eventually leads to efficient surface expression of Kir2.1 channels...
  44. ncbi Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination
    C Neusch
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Neurosci 21:5429-38. 2001
    ..Therefore, this mouse shows how an ion channel mutation could contribute to the polygenic demyelinating diseases...
  45. ncbi Activating mutations in the ABCC8 gene in neonatal diabetes mellitus
    Andrey P Babenko
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
    N Engl J Med 355:456-66. 2006
    ..We hypothesized that activating mutations in ABCC8, which encodes SUR1, cause neonatal diabetes...
  46. pmc Long-chain acyl-CoA esters and phosphatidylinositol phosphates modulate ATP inhibition of KATP channels by the same mechanism
    Dirk Schulze
    Institute of Physiology II, Friedrich Schiller University Jena, Teichgraben 8, 07740 Jena, Germany
    J Physiol 552:357-67. 2003
    ..We provide evidence that CoA and diadenosine polyphosphates (e.g. Ap4A) are ligands of the inhibitory ATP-binding site on Kir6.2...
  47. ncbi ABCC8 and ABCC9: ABC transporters that regulate K+ channels
    Joseph Bryan
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Pflugers Arch 453:703-18. 2007
    ..2 polymorphism has been suggested as a predisposing factor in type 2 diabetes mellitus. Studies on K(ATP) channel null mice are clarifying the roles of these metabolically sensitive channels in a variety of tissues...
  48. ncbi The Walter B. Cannon Physiology in Perspective Lecture, 2007. ATP-sensitive K+ channels and disease: from molecule to malady
    Frances M Ashcroft
    Henry Wellcome Centre for Gene Function, Dept of Physiology, Anatomy and Genetics, Univ of Oxford, Parks Road, Oxford OX1 3PT, UK
    Am J Physiol Endocrinol Metab 293:E880-9. 2007
    ..Here, I review the latest information on the relationship between K(ATP) channel structure and function, and consider how mutations in the K(ATP) channel genes lead to neonatal diabetes or congenital hyperinsulinism...
  49. ncbi Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies
    Coeli M B Lopes
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    Neuron 34:933-44. 2002
    ..We find basic residues that interact with PIP(2), two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP(2) interactions, leading to disease...
  50. pmc Human myoblast fusion requires expression of functional inward rectifier Kir2.1 channels
    J Fischer-Lougheed
    , , CH-1211 Geneva 4, Switzerland
    J Cell Biol 153:677-86. 2001
    ..This hyperpolarization is a prerequisite for fusion, as it sets the resting membrane potential in a range at which Ca2+ can enter myoblasts and thereby trigger fusion via a window current through alpha1H T channels...
  51. ncbi Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation
    Dobromir Dobrev
    Department of Pharmacology and Toxicology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden, Germany
    Cardiovasc Res 54:397-404. 2002
    ..We measured I(K1) and I(K,ACh) in tissue from AF patients with different G beta 3 genotypes and assessed the relation between the I(K1) and I(K,ACh) amplitudes and the incidence of postoperative AF...
  52. ncbi An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway
    Donghui Ma
    Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 282:5781-9. 2007
    ..Based on our functional studies and the cytoplasmic domain crystal structure, we suggest that Val-302 may influence PIP2 gating indirectly by translating PIP2 binding to conformational changes in the G-loop pore...
  53. ncbi Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice
    M Suzuki
    Department of Pharmacology, Chiba University School of Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
    Circ Res 88:570-7. 2001
    ..1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree...
  54. ncbi A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults
    Andrei I Tarasov
    Section of Cell Biology, Division of Medicine, Imperial College London, London, UK
    Diabetes 57:1595-604. 2008
    ..We describe here an activating mutation in the ABCC8 gene, encoding SUR1, that is associated with the development of type 2 diabetes only in adults...
  55. ncbi Kir6.1: a possible subunit of ATP-sensitive K+ channels in mitochondria
    M Suzuki
    Laboratory of Molecular and Cellular Morphology, Gunma University, Japan
    Biochem Biophys Res Commun 241:693-7. 1997
    ..1. These results suggest that Kir6.1 might be a subunit of the ATP-sensitive K+ channel in the mitochondrion, as well as in the plasma membrane...
  56. pmc Stabilization of the activity of ATP-sensitive potassium channels by ion pairs formed between adjacent Kir6.2 subunits
    Yu Wen Lin
    Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, USA
    J Gen Physiol 122:225-37. 2003
    ..The structure lends support to our findings in Kir6.2, and raises the possibility that a homologous ion pair may be involved in the gating of GIRKs...
  57. ncbi Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
    Laura E Parton
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nature 449:228-32. 2007
    ..We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes...
  58. ncbi G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action
    J M Lewohl
    Waggoner Center for Alcohol and Addiction Research and Section on Neurobiology, University of Texas at Austin, Austin, Texas 78712, USA
    Nat Neurosci 2:1084-90. 1999
    G-protein-coupled inwardly rectifying potassium channels (GIRKs) are important for regulation of synaptic transmission and neuronal firing rates...
  59. ncbi Elevated non-esterified fatty acids impair nitric oxide independent vasodilation, in humans: evidence for a role of inwardly rectifying potassium channels
    Saula Vigili de Kreutzenberg
    Department of Clinical and Experimental Medicine, Cattedra di Malattie del Metabolismo, University of Padova, Via Giustiniani 2, 35128 Padua, Italy
    Atherosclerosis 169:147-53. 2003
    ..Ouabain and BaCl(2)-mediated FBF inhibition was lower (P<0.01) at high-NEFA. During ouabain alone FBF decreased slightly...
  60. ncbi Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells
    A P Babenko
    Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX, USA
    Circ Res 83:1132-43. 1998
    ....
  61. pmc Mice transgenically overexpressing sulfonylurea receptor 1 in forebrain resist seizure induction and excitotoxic neuron death
    C Hernandez-Sanchez
    Section on Molecular and Cellular Physiology, Clinical Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:3549-54. 2001
    ..These results indicate that the transgenic overexpression of SUR1 alone in forebrain structures significantly protects mice from seizures and neuronal damage without interfering with locomotor or cognitive function...
  62. ncbi Dynamic sensitivity of ATP-sensitive K(+) channels to ATP
    G Loussouarn
    Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Biol Chem 276:29098-103. 2001
    ..These two mechanisms constitute a feedback system that will tend to render K(ATP) channel activity transiently responsive to a change in [ATP](sub) over a wide range of steady state concentrations...
  63. pmc Nucleotides and phospholipids compete for binding to the C terminus of KATP channels
    Gordon G MacGregor
    Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8026, USA
    Proc Natl Acad Sci U S A 99:2726-31. 2002
    ..Thus the COOH termini of K(ATP) channels form a nucleotide- and phospholipid-modulated channel gate on which ATP and phospholipids compete for binding...
  64. ncbi Molecular structure of the glibenclamide binding site of the beta-cell K(ATP) channel
    M V Mikhailov
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Headington, OX3 9DU, Oxford, UK
    FEBS Lett 499:154-60. 2001
    ..We suggest that in SUR1 in the native K(ATP) channel close proximity of CL3 and CL8 leads to formation of the glibenclamide binding site...
  65. pmc Specificity of activation by phosphoinositides determines lipid regulation of Kir channels
    Tibor Rohacs
    Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 100:745-50. 2003
    ..1 channel decreasing phosphoinositide specificity allow activation by LC acyl-CoA. Our data demonstrate that differences in phosphoinositide specificity determine the modulation of Kir channel activity by distinct regulatory lipids...
  66. pmc On the physiological roles of PIP(2) at cardiac Na+ Ca2+ exchangers and K(ATP) channels: a long journey from membrane biophysics into cell biology
    Donald W Hilgemann
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9040, USA
    J Physiol 582:903-9. 2007
    ..Thus, a better understanding of the regulation of cardiac lipid kinases may be key to understanding when and how cardiac ion transporters and channels are internalized...
  67. ncbi Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects
    Norihide Yokoi
    Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Diabetes 55:2379-86. 2006
    ..This is the largest association study so far conducted on these genes in Japanese and provides valuable information for comparison with other ethnic groups...
  68. pmc Mutations within the P-loop of Kir6.2 modulate the intraburst kinetics of the ATP-sensitive potassium channel
    P Proks
    University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom
    J Gen Physiol 118:341-53. 2001
    ..This gate appears to be able to operate independently of that which regulates the long interburst closings...
  69. pmc Differential structure of atrial and ventricular KATP: atrial KATP channels require SUR1
    Thomas P Flagg
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 103:1458-65. 2008
    ....
  70. ncbi The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis
    Amit S Dhamoon
    Department of Pharmacology and Institute for Cardiovascular Research, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    Heart Rhythm 2:316-24. 2005
    ..The mechanism of channel block, assembly, and structure are reviewed. The article discusses the role of I(K1) in ventricular fibrillation and speculates on modulation of I(K1) as a preventative antiarrhythmic mechanism...
  71. pmc The consequences of disrupting cardiac inwardly rectifying K(+) current (I(K1)) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes
    J J Zaritsky
    Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Stanford, CA 94305, USA
    J Physiol 533:697-710. 2001
    ..1 outside the heart. 5. Thus Kir2.1 is the major component of murine I(K1) and the Kir2.1 (-/-) mouse provides a model in which the functional consequences of removing I(K1) can be studied at both cellular and organismal levels...
  72. pmc AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels
    Andrey Sukhodub
    Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    J Cell Physiol 210:224-36. 2007
    ....
  73. pmc The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel
    Aldo A Rodríguez-Menchaca
    Unidad de Investigación Carlos Méndez del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Mexico
    Proc Natl Acad Sci U S A 105:1364-8. 2008
    ..Moreover, our findings provide the structural framework for the design of safer, alternative compounds that are devoid of Kir2.1-blocking properties...
  74. ncbi Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina
    Thomas Pannicke
    Paul Flechsig Institut für Hirnforschung, Abteilung Neurophysiologie, Universitat Leipzig, Leipzig, Germany
    Glia 50:1-11. 2005
    ..These results suggest a role of altered glial Kir channel expression in postischemic neuronal degeneration via disturbance of retinal K+ siphoning...
  75. pmc Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes
    Heidi de Wet
    Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom
    Proc Natl Acad Sci U S A 104:18988-92. 2007
    ..Molecular modeling studies supported this idea. Because mutant channels were inhibited less strongly by MgATP, this would increase K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes...
  76. ncbi Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells
    Seung K Kim
    Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B300, Stanford, California 94305 5329, USA
    Nature 431:316-20. 2004
    ..Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells...
  77. ncbi A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation
    Min Xia
    Institute of Medical Genetics, Tongji University, Shanghai, China
    Biochem Biophys Res Commun 332:1012-9. 2005
    ..Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel...
  78. pmc KirBac1.1: it's an inward rectifying potassium channel
    Wayland W L Cheng
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Gen Physiol 133:295-305. 2009
    ....
  79. ncbi Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels
    Grit Taschenberger
    Center for Research on Occupational and Environmental Toxicology, The Department of Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 277:17139-46. 2002
    ..Thus, the L1544P mutation may interfere with normal trafficking of K(ATP) channels by causing improper shielding of the RKR endoplasmic reticulum retention/retrieval trafficking signals in the two channel subunits...
  80. pmc 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1
    Michael V Mikhailov
    Laboratory of Physiology, University of Oxford, Oxford, UK
    EMBO J 24:4166-75. 2005
    ..2. The nucleotide-binding domains of adjacent SUR1 appear to interact, and form a large docking platform for cytosolic proteins. The structure, in combination with molecular modelling, suggests how SUR1 interacts with Kir6.2...
  81. ncbi A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels
    N Inagaki
    Division of Molecular Medicine Center for Biomedical Science, Chiba University School of Medicine, Chuo Ku, Chiba 260, Japan
    Neuron 16:1011-7. 1996
    ..The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors...
  82. ncbi Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): interaction with other regulatory ligands
    Lai Hua Xie
    Cardiovascular Research Laboratory, Departments of Medicine Cardiology and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Prog Biophys Mol Biol 94:320-35. 2007
    All members of the inwardly rectifying potassium channels (Kir1-7) are regulated by the membrane phospholipid, phosphatidylinosital-4,5-bisphosphate (PIP(2))...
  83. ncbi Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K+ channels
    Maria S Remedi
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Diabetes 53:3159-67. 2004
    ..We propose an "inverse U" model for the response to enhanced beta-cell excitability: the expected initial hypersecretion can progress to undersecretion and glucose-intolerance, either spontaneously or in response to dietary stress...
  84. ncbi Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma
    C L Huang
    Department of Medicine, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Nature 391:803-6. 1998
    ..Finally, coexpression of Gbetagamma with GIRK channels slows the inhibition of K+ currents by PIP2 antibodies by more than 10-fold. Thus Gbetagamma activates GIRK channels by stabilizing interactions between PIP2 and the K+ channel...
  85. ncbi KATP channel openers: structure-activity relationships and therapeutic potential
    Raimund Mannhold
    Department of Laser Medicine, Molecular Drug Research Group, Heinrich Heine Universitat, Universitatsstrasse 1, 40225 Dusseldorf, Germany
    Med Res Rev 24:213-66. 2004
    ..Examples for new chemical entities more recently developed as KCOs include cyclobutenediones, dihydropyridine related structures, and tertiary carbinols...
  86. ncbi Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators
    Xiaona Du
    Department of Pharmacology, Hebei Medical University, Shijiazhuang, China
    J Biol Chem 279:37271-81. 2004
    ..Furthermore, our results suggest that differences among Kir channels in their specific regulation by a given modulator may reflect differences in their apparent affinity of interactions with PIP(2)...
  87. ncbi K ATP channels of primary human coronary artery endothelial cells consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits
    Hidetada Yoshida
    Department of Pediatric Cardiology, New York University School of Medicine, 560 First Avenue TCH501, New York, NY 10016, USA
    J Mol Cell Cardiol 37:857-69. 2004
    ..We demonstrate that human coronary endothelial K(ATP) channels consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits...
  88. ncbi Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation
    J J Zaritsky
    Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, CA, USA
    Circ Res 87:160-6. 2000
    ..1(-/-) animals did not dilate when the extracellular K(+) concentration was increased to 15 mmol/L. In summary, Kir2.1 gene expression in arterial smooth muscle is required for Kir currents and K(+)-induced dilations in cerebral arteries...
  89. ncbi Changes in I K, ACh single-channel activity with atrial tachycardia remodelling in canine atrial cardiomyocytes
    Niels Voigt
    Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany
    Cardiovasc Res 77:35-43. 2008
    ..This study aimed to establish how AT remodelling affects I K,ACh single-channel function...
  90. pmc Inhibition of electrical activity by retroviral infection with Kir2.1 transgenes disrupts electrical differentiation of motoneurons
    Yone Jung Yoon
    Department of Biology, University of Vermont, Burlington, Vermont, United States of America
    PLoS ONE 3:e2971. 2008
    ..These experiments demonstrate that chronic inhibition of chicken spinal cord activity causes a significant change in the electrical properties of developing motoneurons...
  91. ncbi The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts
    Markus Delling
    Zentrum für Molekulare Neurobiologie, Universitat Hamburg, 20246 Hamburg, Germany
    J Neurosci 22:7154-64. 2002
    ..Thus, regulation of Kir3 channel activity by NCAM may represent a novel mechanism controlling long-term excitability of neurons...
  92. pmc Molecular dissection of the inward rectifier potassium current (IK1) in rabbit cardiomyocytes: evidence for heteromeric co-assembly of Kir2.1 and Kir2.2
    Carsten Zobel
    Departments of Physiology and Medicine, Division of Cardiology, Heart and Stroke Richard Lewar Centre, University Health Network, Toronto, Ontario, Canada
    J Physiol 550:365-72. 2003
    ..Taken together, these results demonstrate functional expression of Kir2.1 and Kir2.2 in rabbit ventricular myocytes and suggest that macroscopic IK1 is predominantly composed of Kir2.1 and Kir2.2 heterotetramers...
  93. ncbi Localization of pore-forming subunit of the ATP-sensitive K(+)-channel, Kir6.2, in rat brain neurons and glial cells
    Ming Zhou
    Department of Anatomy, Akita University School of Medicine, Hondo 1 1 1 Akita 010 8543, Japan
    Brain Res Mol Brain Res 101:23-32. 2002
    ..2. Under the electron microscope, we showed in vivo for the first time that the immunoreactive products were localized in the endoplasmic reticulum and Golgi apparatus as well as the plasma membranes of neurons and glial cells...
  94. pmc Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicing
    Bin Ye
    Department of Medicine, University of Wisconsin, Madison, WI 53706, USA
    Circ Res 105:1083-93. 2009
    ..Cardioprotective pathways may involve a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel but its composition is not fully understood...
  95. pmc Long-pore electrostatics in inward-rectifier potassium channels
    Janice L Robertson
    Program in Physiology, Biophysics and Systems Biology, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA
    J Gen Physiol 132:613-32. 2008
    ..These results provide a foundation for understanding ion interactions in Kir channels and extend to the study of ion permeation, block, and gating in long, cation-specific pores...
  96. ncbi The E23K variant of KCNJ11 and the risk for severe sulfonylurea-induced hypoglycemia in patients with type 2 diabetes
    A Holstein
    First Department of Medicine, Clinic Lippe Detmold, Detmold, Germany
    Horm Metab Res 41:387-90. 2009
    ..Our data suggest that patients with T2D carrying the K variant of the E23K polymorphism in KCNJ11 have reduced response to sulfonylurea therapy, which results in increased HbA(1c) and consequently in lower risk for SH...
  97. ncbi Role of glial K(+) channels in ontogeny and gliosis: a hypothesis based upon studies on Müller cells
    A Bringmann
    Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany
    Glia 29:35-44. 2000
    ..It is concluded that in respect to their K(+) current pattern, mature Müller cells pass through a process of dedifferentiation before proliferative activity is initiated...
  98. ncbi Ion channel gates: comparative analysis of energy barriers
    Kaihsu Tai
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
    Eur Biophys J 38:347-54. 2009
    ..In general, the method is more useful when the channel is wider; for narrower channels, the flexibility of the protein may allow otherwise-unsurmountable energetic barriers to be overcome...
  99. ncbi ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury
    T Kawano
    Department of Anesthesiology, Anesthesia Research MEB, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Neuroscience 162:431-43. 2009
    ..Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain...
  100. pmc Insulin gene mutations as a cause of permanent neonatal diabetes
    Julie Støy
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 104:15040-4. 2007
    ..One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder...
  101. ncbi Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene
    G Tonini
    Diabetologia 49:2210-3. 2006

Research Grants63

  1. Epigenetic Regulation of Kir4.1 and GLT1 in Pathophysiology
    Michelle L Olsen; Fiscal Year: 2013
    ..Results from these experiments could lead to novel therapeutic strategies using FDA-approved drugs for the treatment of TBI in pediatric patients. ..
  2. GENETIC VULNERABILITY TO DRUGS OF ABUSE
    Kari J Buck; Fiscal Year: 2013
    ..This can direct further mechanistic studies and elucidate the important network(s), within which many biomarkers and drugable targets may exist to direct translational studies. ..
  3. Molecular Regulation of Cardiac KATP Channels in Ischemia
    Jonathan C Makielski; Fiscal Year: 2013
    ..The results may suggest more specific therapeutic targets in the SUR2 variants, and it will also provide important new information on mitochondrial structure and function in heart. ..
  4. CELLULAR INFORMATION PROCESSING IN THE HIPPOCAMPUS
    Daniel Johnston; Fiscal Year: 2013
    ..The experiments will utilize hippocampal brain slices from rats, somatic and dendritic patch-clamp electrophysiology, and immunohistochemistry and western blotting. ..
  5. Persistent Pain and Opioid Mechanisms in the Rostroventral Medial Medulla
    MARLENE CANO; Fiscal Year: 2011
    ....
  6. Gene-based Neuromodulation: A New Paradigm for Functional Neurosurgery
    Nicholas M Boulis; Fiscal Year: 2012
    ..3) The Rheoswitch(r) inducible expression system will improve controlled LC delivery. 4) Neuronal Kir2.1 gene expression can safely inhibit neuronal activity with potency exceeding that of LC mediated synaptic inhibition. ..
  7. OPIOID RECEPTOR MECHANISMS
    John R Traynor; Fiscal Year: 2010
    ..An understanding of roles for RGS proteins in the actions of mu-opioids may lead to improvements in the treatment of pain as well as treatment of opioid and stimulant abuse. ..
  8. Structural analysis of alcohol-dependent activation of GIRKs
    Paul A Slesinger; Fiscal Year: 2013
    ..with high-resolution structural studies that alcohols bind directly to hydrophobic pockets of inwardly rectifying potassium channels. Mutations in the alcohol-binding pocket of GIRK2 channels significantly alter ethanol activation...
  9. G protein regulation of inwardly rectifying potassium channels
    Rahul Mahajan; Fiscal Year: 2012
    ..Most drugs sold today directly or indirectly modulate G protein signaling. Thus enhanced knowledge of the structural mechanisms underlying this signaling may reveal further targets for manipulation by therapy. ..
  10. GENETIC STUDIES OF THE SYNAPSE
    Lily Jan; Fiscal Year: 2000
    ..This proposed study concerns structure- function analysis of the inwardly rectifying potassium channels which became amenable to molecular studies last year...
  11. MUSCARINIC AND ADENOSINE RECEPTOR SIGNAL TRANSDUCTION
    Richard Mortensen; Fiscal Year: 2001
    ..sensitive G-proteins to directly and indirectly (via second messengers) regulate ion channels (inwardly rectifying potassium channels, acetylcholine activated potassium channels, L-type calcium channels, and pacemaker channels)...
  12. CONTROL OF GLUTAMATE RECEPTOR ACTIVATION
    Stephen Traynelis; Fiscal Year: 2006
    ..Finally, we will determine at the single channel level the mechanisms of action of a non-competitive and therapeutically interesting class of antagonists - phenylethanolamines, such as ifenprodil. ..
  13. CANNABINOID MODULATION OF NEURONAL FUNCTION
    Kenneth Mackie; Fiscal Year: 2005
    ..Specifically, they inhibit and Q-type voltage-dependent calcium channels and activate inwardly rectifying potassium channels. Consistent with these actions, cannabinoids decrease neuronal excitability and neurotransmission ..
  14. Development of Gene Therapy for Chronic Pain
    David Johns; Fiscal Year: 2005
    ..In conclusion, our proposal will look to combine improved vector development with novel recording techniques to monitor closely the efficacy of gene transfer and to also assess these treatments behaviorally in animals. ..
  15. Mechanisms of seizure propagation in limbic cortex
    LEWIS HABERLY; Fiscal Year: 2007
    ..These experiments will provide essential information about the spread of epileptic activity into normal cortex, and clues concerning how this spread can be curtailed. ..
  16. HETEROMULTIMERIZATION AND REGULATION OF RENAL K CHANNELS
    Wade Pearson; Fiscal Year: 2002
    ..We hypothesize that the mechanism, designated "K+ regulation," will have significant physiological implications not only for epithelial cells in the nephron, but also for excitable cells such as muscle cells and neurons. ..
  17. INTRACELLULAR MESSENGERS--BIOPHYSICAL STUDIES
    Henry Lester; Fiscal Year: 2002
    ..G protein-gated K+ channels (GIRKs) control the strength and frequency of the heartbeat, some responses to drugs of therapy and abuse, and some aspects of insulin secretion. ..
  18. PROTEIN KINASE C AND THE COUPLING OF 5-HT1A RECEPTORS
    NICHOLAS PENINGTON; Fiscal Year: 2000
    ..3) To investigate whether these observations can be observed in a more physiological setting, by examining the effect of 5-HT and phorbol esters on the Ca2+ activated K+ conductance of DR neurons in the slice preparation. ..
  19. MUSCARINIC GATED ATRIAL K+ CHANNEL
    Deborah Nelson; Fiscal Year: 1999
    ..the structural elements involved in coupling between G proteins and this important class of inwardly rectifying potassium channels. In a broader sense, the high resolution measurements achievable in these types of experiments may ..
  20. POTASSIUM HOMEOSTASTASIS OF KV 1.3-DEFICIENT MICE
    Jianchao Xu; Fiscal Year: 2005
    ..3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse. ..
  21. IONIC MECHANISMS RELATED TO SECRETION IN PITUITARY CELLS
    GERRY OXFORD; Fiscal Year: 2002
    ....
  22. REGULATION OF INWARD RECTIFIER POTASSIUM CHANNELS
    Arthur Brown; Fiscal Year: 2000
    ..Functional tests using patch clamp are performed simultaneously. For the second part of Aim 5, a variety of candidate modifier subunits that we have cloned will be tested for their ability to make hIRK more closely mimic I-Kr. ..
  23. Neuroendo Signal Transduction in Reproductive Physiology
    KAREN GREGERSON; Fiscal Year: 2007
    ..Such studies will ultimately provide insight into the basis of secretory disorders in PRL, a hormone at the core of mammalian fertility, gestation and lactation. ..
  24. Advanced Isotope Aided NMR For CB2 Structural Study
    Xiang Qun Xie; Fiscal Year: 2005
    ..The work accomplished through this proposed research can potentially make a significant contribution to cannabinoid research and NMR structural biology, as well as GPCRs in general. ..
  25. Permeation and Gating of Inwardly-Rectifying Potassium Channels.
    Harley Kurata; Fiscal Year: 2009
    ..A detailed understanding of the fundamental mechanisms of Kir channel regulation will provide a basis for ultimately developing interventions to regulate disorders of electrical excitability in the heart, vasculature, and beyond. ..
  26. CANNABINOID AGONIST REGULATION OF SIGNAL TRANSDUCTION
    PAUL PRATHER; Fiscal Year: 2004
    ..of voltage-dependent calcium currents, activation of MAPK activity and finally, activation of inwardly rectifying potassium channels. The third portion of this aim involves identifying the specific G protein alpha subunits ..
  27. GATING OF INWARDLY RECTIFYING POTASSIUM CHANNELS
    Zheng Fan; Fiscal Year: 2003
    ....
  28. MOLECULAR BIOLOGY OF CARDIAC ION CHANNELS
    Arthur Brown; Fiscal Year: 1991
    ..This project will provide important insights into molecules that are essential for the cardiac impulse. This understanding should be useful in the treatment of cardiac arrhythmias which are the commonest cause of death...
  29. Glial Maintenance of Local K+ and Neurotransmission
    JULIAN MEEKS; Fiscal Year: 2005
    ..These studies will determine the functional relevance of KIRs in hippocampal astrocytes and provide new insight into the role of KIRs in passive [K+]o buffering. ..
  30. BIOGENESIS AND MATURATION OF INWARD RECTIFIER K CHANNELS
    Kevin Ho; Fiscal Year: 1999
    ..abstract_text> ..
  31. ASSEMBLY OF INWARD RECTIFIER K CHANNELS
    Kevin Ho; Fiscal Year: 1999
    ..Oligomerization and localization will be studied by sucrose gradient centrifugation, immunoprecipitation, immunoblotting, confocal microscopy, and functional expression in Xenopus oocytes and baculovirus-infected Sf-9 cells. ..
  32. Activity-dependent regulation of neuronal GIRK channels
    HEE CHUNG; Fiscal Year: 2007
    ..These studies will reveal novel mechanisms for modulating inhibitory synaptic function [unreadable] [unreadable]..
  33. MOLECULAR PHYSIOLOGY OF CARDIAC POTASSIUM CHANNELS
    CAROL VANDENBERG; Fiscal Year: 2000
    ..The goal of this project is an understanding of the molecular basis of the structure and function of inwardly rectifying potassium channels. These channels are central to the functioning of cardiac cells where they are involved in ..
  34. Eukaryotic Ion Channel Expression for Structural Study
    DANIEL MINOR; Fiscal Year: 2005
    ..The methods developed here are general and, once established, should permit the overproduction of a wide range of ion channels as well as other eukaryotic membrane proteins for biochemical and structural study. ..
  35. MODELS OF OPIOID RECEPTOR DESENSITIZATION MECHANISMS
    Charles Chavkin; Fiscal Year: 2003
    ..by defining the effects of specific kinases on the coupling between opioid receptor activation and inwardly rectifying potassium channels heterologously expressed in Xenopus oocytes, by comparing the effects of specific receptor ..
  36. Reactive astrocytes from gliotic capsule
    J Marc Simard; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  37. CEREBROVASCULAR ION CHANNELS IN HYPERTENSION
    J Marc Simard; Fiscal Year: 2007
    ..abstract_text> ..
  38. PATHOPHYSIOLOGY OF NICOTINE IN CEREBRAL BLOOD VESSELS
    J Simard; Fiscal Year: 2004
    ....
  39. MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELS
    Zhe Lu; Fiscal Year: 2002
    ..For example, G-protein gated inward-rectifier K+ channels mediate the regulation of heart rate by vagal nerve, and ATP-sensitive inward-rectifier K+ channels are important during cardiac ischemia. (End of Abstract) ..
  40. Development and study of specific Kir channel inhibitors
    Zhe Lu; Fiscal Year: 2009
    ..abstract_text> ..
  41. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2007
    ....
  42. 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. ..
  43. INNER RETINAL CONTRIBUTIONS TO THE ERG
    Bret Hughes; Fiscal Year: 2003
    ....
  44. 9th International Workshop on Developmental Nephrology
    Lisa Satlin; Fiscal Year: 2004
    ..The meeting will be held at Barossa Valley Resort, an optimal venue for such interaction, immediately preceding the 13th IPNA Congress in Adelaide, South Australia (August 29-September 2, 2004). ..
  45. KIR channel modulations in hypercapnic acidosis
    Chun Jiang; Fiscal Year: 2004
    ....
  46. TRAINING IN DEVELOPMENTAL BIOLOGY OF MEMBRANE TRANSPORT
    Lisa Satlin; Fiscal Year: 2004
    ..All candidates for this training program will be expected to devote a minimum of three years to research training. ..
  47. Vascular KATP Channel Modulation in Hypercapnic Acidosis
    Chun Jiang; Fiscal Year: 2006
    ..abstract_text> ..
  48. ROMK CHANNEL FUNCTION AND REGULATION IN KIDNEY
    Gerhard Giebisch; Fiscal Year: 2003
    ..Patch-clamp and whole-cell current measurements will be carried out in native tubules and in an oocyte expression system, and tubule perfusion studies in ROMK knock-out mice. ..
  49. Pathophysiology of ARPKD: role of aberrant transport
    Lisa Satlin; Fiscal Year: 2002
    ..Parallel studies will also be performed in the orpk murine model of ARPKD, whose microdissected tubules can be isolated and microperfused in vitro. ..
  50. Chemical Synapses - Biophysical Studies
    Henry Lester; Fiscal Year: 2009
    ..abstract_text> ..
  51. Selective Silencing of Mammalian Neurons: Proof of Mice
    Henry Lester; Fiscal Year: 2004
    ..If the "proof of concept" experiments succeed, an R01 grant will be sought to extend and exploit the system. There are important applications in many fields of neuroscience. ..
  52. BIAcore 3000 System
    LESLIE GRIFFITH; Fiscal Year: 2002
    ..The salary of the Principal Operator, as well as space in the Facility, and funds for maintenance of the instrument are guaranteed into the foreseeable future. ..
  53. METABOTROPIC GLUTAMATE RECEPTORS IN BASAL GANGLIA
    COLLEEN NISWENDER; Fiscal Year: 2009
    ..Furthermore, we will test the hypothesis that agonists or allosteric potentiators of this receptor can provide palliative relief in rodent models of PD by actions in the GP. ..
  54. TRPM4 Channels in the Control of Cerebral Artery Tone
    Scott Earley; Fiscal Year: 2005
    ..It is anticipated that these studies will generate significant new information regarding the role of mechanosensitive cation channels in the regulation of VSM membrane potential and the regulation of cerebral blood flow. ..
  55. SPATIO-TEMPORAL PERIODICITY IN ARTIAL FIBRILLATION
    JOSE JALIFE; Fiscal Year: 2006
    ..Accomplishment of the proposed studies should lead to an increased understanding of the mechanisms of AF at the molecular, cellular and organ levels and may lead to therapeutic advances. [unreadable] [unreadable]..
  56. Autosomal dominant nocturnal frontal-lobe epilepsy
    Henry Lester; Fiscal Year: 2004
    ....
  57. Neuromodulation of Voltage-gated Ca2+ Channels
    Jian Yang; Fiscal Year: 2007
    ..This research may not only enhance our understanding of the complex regulatory pathways for VGCCs but also provide valuable information for the development of potential therapeutic reagents that target these pathways ..
  58. Human Beta Cell Parameters for Islet Engraftment Success
    Peter Drain; Fiscal Year: 2005
    ..The knowledge from these studies can be applied to improve reliability of clinical engraftments. ..
  59. CYTOSOLIC REGULATION OF INNER EAR ION TRANSPORT
    A PHILINE WANGEMANN; Fiscal Year: 2007
    ..first, middle) The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  60. The Genetic Basis of Atrial Fibrillation
    Patrick Ellinor; Fiscal Year: 2007
    ..Fishman. [] PHS 39812590 (Rev. 05101) Page % Continuation Format Page o Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. ..
  61. GABAergic excitation in human hypothalamic hamartoma
    Jie Wu; Fiscal Year: 2007
    ..Knowledge about excitatory GABAA receptor function of HH neurons will also aid selection of superior strategies for pharmaceutical development to prevent and control human gelastic seizures. [unreadable] [unreadable]..
  62. Metabolism-excitation coupling in the heart
    Colin Nichols; Fiscal Year: 2005
    ..The work will provide information that will ultimately underlie the development of rational therapies for the treatment of cardiac ischemia and arrhythmias. ..
  63. Voltage Sensor Movement in the HERG Potassium Channel
    Martin Tristani Firouzi; Fiscal Year: 2008
    ..abstract_text> ..