myotonia

Summary

Summary: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.

Top Publications

  1. ncbi Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice
    C A Gurnett
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA
    J Biol Chem 270:9035-8. 1995
  2. pmc Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 103:11748-53. 2006
  3. pmc Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block
    Jean Francois Desaphy
    Division of Pharmacology, Department of Pharmaco Biology, University of Bari, Bari I 70125, Italy
    J Physiol 554:321-34. 2004
  4. pmc The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment
    E Matthews
    MRC Centre for Neuromuscular Diseases, UCL, Institute of Neurology, Queen Square, London, WC1N 3BG, England
    Brain 133:9-22. 2010
  5. pmc Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial
    Jeffrey M Statland
    Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
    JAMA 308:1357-65. 2012
  6. pmc Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 118:1437-49. 2008
  7. pmc Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia
    C Meyer-Kleine
    Medizinisches Zentrum für Humangenetik, Philipps Universitat Marburg, Federal Republic of Germany
    Am J Hum Genet 57:1325-34. 1995
  8. ncbi Novel chloride channel mutations leading to mild myotonia among Chinese
    Jean Marc Burgunder
    Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Neuromuscul Disord 18:633-40. 2008
  9. ncbi Characterization of two new dominant ClC-1 channel mutations associated with myotonia
    Morten Grunnet
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Muscle Nerve 28:722-32. 2003
  10. ncbi Equine muscular dystrophy with myotonia
    P Montagna
    Institute of Clinical Neurology, University of Bologna Medical School, Via U Foscolo 7, 40123, Bologna, Italy
    Clin Neurophysiol 112:294-9. 2001

Research Grants

Detail Information

Publications191 found, 100 shown here

  1. ncbi Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice
    C A Gurnett
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA
    J Biol Chem 270:9035-8. 1995
    ..Mutations in the ClC-1 gene are responsible for both human autosomal recessive generalized myotonia and autosomal dominant myotonia congenita...
  2. pmc Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 103:11748-53. 2006
    ..muscle with a recombinant adeno-associated viral vector rescues disease-associated muscle hyperexcitability, or myotonia, in the HSA(LR) poly(CUG) mouse model for DM...
  3. pmc Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block
    Jean Francois Desaphy
    Division of Pharmacology, Department of Pharmaco Biology, University of Bari, Bari I 70125, Italy
    J Physiol 554:321-34. 2004
    Flecainide, a class IC antiarrhythmic, was shown to improve myotonia caused by sodium channel mutations in situations where the class IB antiarrhythmic drug mexiletine was less efficient...
  4. pmc The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment
    E Matthews
    MRC Centre for Neuromuscular Diseases, UCL, Institute of Neurology, Queen Square, London, WC1N 3BG, England
    Brain 133:9-22. 2010
    ..Many distinct clinical phenotypes are now recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness...
  5. pmc Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial
    Jeffrey M Statland
    Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
    JAMA 308:1357-65. 2012
    ..Mexiletine-induced sodium channel blockade reduced myotonia in small studies; however, as is common in rare diseases, larger studies of safety and efficacy have not ..
  6. pmc Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 118:1437-49. 2008
    Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion...
  7. pmc Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia
    C Meyer-Kleine
    Medizinisches Zentrum für Humangenetik, Philipps Universitat Marburg, Federal Republic of Germany
    Am J Hum Genet 57:1325-34. 1995
    Autosomal dominant myotonia congenita and autosomal recessive generalized myotonia (GM) are genetic disorders characterized by the symptom of myotonia, which is based on an electrical instability of the muscle fiber membrane...
  8. ncbi Novel chloride channel mutations leading to mild myotonia among Chinese
    Jean Marc Burgunder
    Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Neuromuscul Disord 18:633-40. 2008
    We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found...
  9. ncbi Characterization of two new dominant ClC-1 channel mutations associated with myotonia
    Morten Grunnet
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Muscle Nerve 28:722-32. 2003
    ..More than 60 CLCN1 mutations have been associated with myotonia congenita...
  10. ncbi Equine muscular dystrophy with myotonia
    P Montagna
    Institute of Clinical Neurology, University of Bologna Medical School, Via U Foscolo 7, 40123, Bologna, Italy
    Clin Neurophysiol 112:294-9. 2001
    To describe a case of equine muscular dystrophy with myotonia.
  11. ncbi Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation
    Futoshi Aoike
    Department of Neurology, Osaka University Graduate School of Medicine D 4, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Eur J Pharmacol 532:24-31. 2006
    Flecainide, a class Ic antiarrhythmic drug, has been anecdotally reported to improve myotonia, but little is known about its kinetics on human skeletal muscle sodium channels applicable in vivo...
  12. pmc An interactive voice response diary for patients with non-dystrophic myotonia
    Jeffrey M Statland
    Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
    Muscle Nerve 44:30-5. 2011
    Non-dystrophic myotonia (NDM) is caused by mutations in muscle chloride and sodium channels. Currently, there is no standardized instrument for documenting symptom frequency and severity in NDM.
  13. pmc Non-dystrophic myotonia: prospective study of objective and patient reported outcomes
    Jaya R Trivedi
    Department of Neurology and Neurotherapeutics, UT Southwestern Medical Centre, Dallas, TX 75390, USA
    Brain 136:2189-200. 2013
    ..Few prospective studies have evaluated the sensitivity of symptoms and signs of myotonia in a large cohort of patients...
  14. ncbi Treatment of myotonia with antiarrhythmic drugs
    H Kwiecinski
    Department of Neurology, Warsaw Medical Academy, Poland
    Acta Neurol Scand 86:371-5. 1992
    ..The severity of myotonia was assessed by clinical and electromyographic criteria at the end of each treatment phase lasting four weeks...
  15. ncbi A sodium channel myotonia due to a novel SCN4A mutation accompanied by acquired autoimmune myasthenia gravis
    Yosuke Kokunai
    Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
    Neurosci Lett 519:67-72. 2012
    Mutations of the voltage gated sodium channel gene (SCN4A) are responsible for non-dystrophic myotonia including hyperkalemic periodic paralysis, paramyotonia congenita, and sodium channel myotonia, as well as congenital myasthenic ..
  16. ncbi A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes
    Harumi Yoshinaga
    Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    J Neurol Sci 315:15-9. 2012
    ..channel (SCN4A) are responsible for hyperkalemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are classified based on their cardinal symptoms, myotonia and/or paralysis...
  17. ncbi Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene
    María J Mazón
    Instituto de Investigaciones Biomedicas Alberto Sols, Departamento de Bioquimica, CSIC UAM, Madrid, Spain
    Neuromuscul Disord 22:231-43. 2012
    b>Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle...
  18. ncbi Electrical myotonia and cataract in X-linked muscular dystrophy (mdx) mouse
    T Kurihara
    Fourth Department of Medicine, Toho University School of Medicine, Tokyo, Japan
    J Neurol Sci 99:83-92. 1990
    ..recordings from the mdx mouse hemidiaphragm preparations revealed low resting membrane potentials and electrical myotonia which occurred at the time of microelectrode insertion and withdrawal...
  19. pmc In vivo evaluation of antimyotonic efficacy of β-adrenergic drugs in a rat model of myotonia
    Jean Francois Desaphy
    Section of Pharmacology, Department of Pharmacy, University of Bari Aldo Moro, Via Orabona 4 Campus, 70125 Bari, Italy
    Neuropharmacology 65:21-7. 2013
    ..We now developed a pharmacological rat model of myotonia congenita to perform in vivo preclinical test of antimyotonic drugs. Myotonia was induced by i.p...
  20. pmc Diagnostics and therapy of muscle channelopathies--Guidelines of the Ulm Muscle Centre
    F Lehmann-Horn
    Institute of Applied Physiology, Ulm University, Ulm, Germany
    Acta Myol 27:98-113. 2008
    ..state-of-the-art diagnostics and therapies for the two types of myotonic dystrophies, for recessive and dominant myotonia congenita, for the sodium channel myotonias, for the primary dyskalemic periodic paralyses, for central core ..
  21. ncbi Cold extends electromyography distinction between ion channel mutations causing myotonia
    Emmanuel Fournier
    Fédération de Neurophysiologie Clinique, Groupe Hospitalier Pitie Salpetriere, Assistance Publique Hopitaux de Paris, Universite Pierre et Marie Curie, Paris
    Ann Neurol 60:356-65. 2006
    ..Nondystrophic forms are caused by mutations in genes coding for the muscle chloride or sodium channel. Myotonia is either relieved or worsened by repeated exercise and can merge into flaccid weakness during exposure to cold, ..
  22. pmc Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker
    H Lerche
    Department of Applied Physiology, University of Ulm, Germany
    J Physiol 470:13-22. 1993
    1. Three families with a form of myotonia (muscle stiffness due to membrane hyperexcitability) clinically distinct from previously classified myotonias were examined. The severity of the disease greatly differed among the families. 2...
  23. ncbi A novel SCN4A mutation causing myotonia aggravated by cold and potassium
    R Heine
    Department of Applied Physiology, University of Ulm, Germany
    Hum Mol Genet 2:1349-53. 1993
    The single strand conformation polymorphism (SSCP) technique was used to screen genomic DNA of a family with myotonia aggravated by cold, potassium loading and suxamethonium, but without muscle weakness...
  24. ncbi A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian cattle dog
    Daniel F Finnigan
    Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada
    J Vet Intern Med 21:458-63. 2007
    Heritable myotonia is a genetic muscle disorder characterized by slow relaxation of skeletal muscles. The main clinical signs are skeletal muscle stiffness, especially after vigorous contraction, and muscle hypertrophy...
  25. pmc Molecular basis for decreased muscle chloride conductance in the myotonic goat
    C L Beck
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 2372, USA
    Proc Natl Acad Sci U S A 93:11248-52. 1996
    Certain forms of myotonia, a condition characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability, are caused by diminished chloride conductance in the muscle cell membrane...
  26. ncbi Mutual interference of myotonia and muscular dystrophy in the mouse: a study on ADR-MDX double mutants
    P Heimann
    Developmental Biology Molecular Pathology, University of Bielefeld, Germany
    Neuromuscul Disord 8:551-60. 1998
    For Duchenne muscular dystrophy (DMD, dystrophin deficiency) and Thomsen/Becker myotonia (muscular chloride channel deficiency) genetically homologous mouse models are available, the dystrophin-deficient MDX mouse and the myotonic ADR ..
  27. ncbi A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians
    E Rossignol
    Laboratory of Neurogenetics of Motion, Universite de Montreal, Montreal, Canada
    Neurology 69:1937-41. 2007
    b>Myotonia is observed in classic congenital myotonia caused by CLCN1 mutations and in sodium-channel myotonia (SCM) due to SCN4A mutations.
  28. ncbi The myotonic mouse mutant ADR: physiological and histochemical properties of muscle
    J Reininghaus
    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany
    Muscle Nerve 11:433-9. 1988
    ..These physiological data suggest that ADR is a myotonia. With a few exceptions, limb and trunk muscles of ADR animals showed a uniform oxidative phenotype with a lack of ..
  29. ncbi The myotonic mouse mutant ADR: electrophysiology of the muscle fiber
    G Mehrke
    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany
    Muscle Nerve 11:440-6. 1988
    ..4 times longer. This finding indicated a drastic reduction of chloride conductance of the ADR muscle membrane. We conclude that ADR is a myotonia, related in its etiology to hereditary myotonias of man.
  30. ncbi K-aggravated myotonia mutations at residue G1306 differentially alter deactivation gating of human skeletal muscle sodium channels
    James R Groome
    Department of Biology, Idaho State University, Pocatello, ID, 83209 8007, USA
    Cell Mol Neurobiol 25:1075-92. 2005
    ..4) and potassium-aggravated myotonia (PAM) mutations G1306A, G1306E, and G1306V...
  31. ncbi Genetic CLC-1 chloride channel deficiency modifies diaphragm muscle isometric contractile properties
    Erik van Lunteren
    Pulmonary and Critical Care Medicine, Case Western Reserve University, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA
    Respir Physiol Neurobiol 155:220-6. 2007
    Genetic deficiency of the muscle chloride channel CLC-1 leads to myotonia congenita in humans as well as myotonia in mice and goats...
  32. ncbi A new mutation in a family with cold-aggravated myotonia disrupts Na(+) channel inactivation
    F F Wu
    Department of Human Genetics, University of Pittsburgh, PA, USA
    Neurology 56:878-84. 2001
    OBJECTIVE: To identify the molecular and physiologic abnormality in familial myotonia with cold sensitivity, hypertrophy, and no weakness...
  33. ncbi Myotonia caused by mutations in the muscle chloride channel gene CLCN1
    Michael Pusch
    Istituto di Cibernetica e Biofisica, CNR, Genova, Italy
    Hum Mutat 19:423-34. 2002
    Pure non-syndromic, non-dystrophic myotonia in humans is caused by mutations in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes...
  34. pmc A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation
    Fen fen Wu
    Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9036, USA
    J Physiol 565:371-80. 2005
    ..A patient with cold-aggravated myotonia did not harbour any of the common SCN4A mutations...
  35. pmc Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker)
    M C Koch
    Medizinisches Zentrum für Humangenetik, Philipps Universitat Marburg, Germany
    J Med Genet 30:914-7. 1993
    Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal muscles with marked hypertrophy in the legs...
  36. pmc Developmental control of the excitability of muscle: transplantation experiments on a myotonic mouse mutant
    E M Füchtbauer
    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany
    Proc Natl Acad Sci U S A 85:3880-4. 1988
    Developmental aspects of an animal model of myotonia, the mouse mutant called "arrested development of righting response" (ADR phenotype), were studied...
  37. ncbi A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia
    S Petitprez
    Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
    Neurology 71:1669-75. 2008
    Mutations in SCN4A may lead to myotonia.
  38. pmc Familial cramp due to potassium-aggravated myotonia
    R W Orrell
    Department of Neuromuscular Diseases, Imperial College School of Medicine, Charing Cross Hospital, London, UK
    J Neurol Neurosurg Psychiatry 65:569-72. 1998
    ..the skeletal muscle sodium channel gene in both patients, consistent with the diagnosis of potassium-aggravated myotonia. The phenotype in this family is much milder than that previously described in another family with a mutation at ..
  39. pmc Isolated eyelid closure myotonia in two families with sodium channel myotonia
    B C Stunnenberg
    Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Neurogenetics 11:257-60. 2010
    ..myotonic syndromes (NDMs), reflect a heterogeneous group of clinical phenotypes accompanied by a generalized myotonia. Because of recent availability of diagnostic genetic testing in NDM, there is a need for identification of clear ..
  40. pmc Myotonia-related mutations in the distal C-terminus of ClC-1 and ClC-0 chloride channels affect the structure of a poly-proline helix
    Maria J Macias
    Institut de Recerca Biomèdica, Parc Cientific de Barcelona, Josep Samitier 1 5, Barcelona, E 08028, Spain
    Biochem J 403:79-87. 2007
    b>Myotonia is a state of hyperexcitability of skeletal-muscle fibres. Mutations in the ClC-1 Cl- channel cause recessive and dominant forms of this disease...
  41. ncbi Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians
    Nicolas Dupre
    Department of Neurological Sciences, CHAUQ Enfant Jésus, Faculty of Medicine, Laval University, Quebec City, QC, Canada
    Neuromuscul Disord 19:330-4. 2009
    Thirty-three French-Canadian families with non-dystrophic myotonia were identified. Fifty subjects were recruited and submitted to a complete clinical, electrophysiologic and genetic evaluation...
  42. ncbi Myotonia and disorders of altered muscle cell membrane excitability
    Charles H Vite
    Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Vet Clin North Am Small Anim Pract 32:169-87, vii. 2002
    ..Hyperexcitability of the sarcolemma results in myotonia, and hypoexcitability results in paresis or paralysis...
  43. pmc A novel alteration of muscle chloride channel gating in myotonia levior
    Aisling Ryan
    Department of General Physiology, University of Ulm, 89069 Ulm, Germany
    J Physiol 545:345-54. 2002
    Mutations in the voltage-dependent skeletal muscle chloride channel, ClC-1, result in dominant or recessive myotonia congenita. The Q552R mutation causes a variant of dominant myotonia with a milder phenotype, myotonia levior...
  44. ncbi Myotonia levior is a chloride channel disorder
    F Lehmann-Horn
    Department of Applied Physiology, University of Ulm, Germany
    Hum Mol Genet 4:1397-402. 1995
    ..Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized ..
  45. pmc A mutation in a rare type of intron in a sodium-channel gene results in aberrant splicing and causes myotonia
    Tomoya Kubota
    Department of Neurology, Osaka University Graduate School of Medicine, 2 2 Yamadaoaka, Suita, Osaka, Japan
    Hum Mutat 32:773-82. 2011
    Many mutations in the skeletal-muscle sodium-channel gene SCN4A have been associated with myotonia and/or periodic paralysis, but so far all of these mutations are located in exons...
  46. ncbi Inactivation of muscle chloride channel by transposon insertion in myotonic mice
    K Steinmeyer
    Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
    Nature 354:304-8. 1991
    b>MYOTONIA (stiffness and impaired relaxation of skeletal muscle) is a symptom of several diseases caused by repetitive firing of action potentials in muscle membranes...
  47. pmc Fatigue-inducing stimulation resolves myotonia in a drug-induced model
    Erik van Lunteren
    Pulmonary and Critical Care Medicine, Case Western Reserve University and Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA
    BMC Physiol 11:5. 2011
    Slowed muscle relaxation is the contractile hallmark of myotonia congenita, a disease caused by genetic CLC-1 chloride channel deficiency, which improves with antecedent brief contractions ("warm-up phenomenon")...
  48. ncbi Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation
    Veronique Bissay
    Department of Neurology, UZ Brussel, Vrije Universiteit Brussel VUB, Belgium
    Neuromuscul Disord 21:590-3. 2011
    We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia...
  49. pmc Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids
    S H Bryant
    J Physiol 219:367-83. 1971
    ..It is concluded that these compounds block chloride conductance.4. The carboxylic acids produced myotonia in normal fibres similar to that in untreated myotonic fibres.5...
  50. ncbi Development of electrical myotonia in the ADR mouse: role of chloride conductance in myotubes and neonatal animals
    E Wischmeyer
    Developmental Biology Unit, University of Bielefeld, Germany
    Neuromuscul Disord 3:267-74. 1993
    ..condition of the autosomal mutation adr, "arrested development of righting response", leads to the symptoms of myotonia. The adr mutation is caused by an insertion of a retroposon into a gene for a chloride channel (adr = Clc-1) that ..
  51. ncbi Malignant hyperthermia and myotonic disorders
    Harvey K Rosenbaum
    UCLA Department of Anesthesiology, UCLA Malignant Hyperthermia Program, Box 951778, Los Angeles, CA 90095 1778, USA
    Anesthesiol Clin North America 20:623-664. 2002
    ..For example, myotonia or profound weakness may be observed in sodium channel disease (e.g...
  52. ncbi Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome
    M Zaki
    Prenatal Diagnosis Unit, Women s Centre, Oxford Radcliffe Hospital, Headington, Oxford, UK
    Ultrasound Obstet Gynecol 29:284-8. 2007
    ..The objective of this study was to assess the maternal and prenatal ultrasound findings and outcome in pregnancies complicated by congenital myotonic dystrophy Type 1 (DM1)...
  53. ncbi Skeletal muscle channelopathies
    Karin Jurkat-Rott
    Department of Applied Physiology, University of Ulm, 89069 Ulm, Germany
    J Neurol 249:1493-502. 2002
    ..are associated with mutations in voltage-gated Na(+), K(+), Ca(2+), and Cl(-) channels leading to hypoexcitability, causing periodic paralysis and to hyperexcitabilty, resulting in myotonia or susceptibility to malignant hyperthermia.
  54. pmc Warm-up phenomenon in myotonia associated with the V445M sodium channel mutation
    J Trip
    J Neurol 254:257-8. 2007
  55. ncbi "Slow" myotonic discharges
    Paul E Barkhaus
    Muscle Nerve 34:799-800. 2006
  56. pmc Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy
    Mani S Mahadevan
    Department of Pathology, University of Virginia, PO Box 800904, Charlottesville, Virginia 22908 0904, USA
    Nat Genet 38:1066-70. 2006
    ..that mice overexpressing a normal DMPK 3' UTR mRNA reproduced cardinal features of myotonic dystrophy, including myotonia, cardiac conduction abnormalities, histopathology and RNA splicing defects in the absence of detectable nuclear ..
  57. ncbi [A girl with hereditary myotonia due to an exceptional sodium channel mutation]
    J C van den Bergen
    afd Klinische Genetica, Universitair Medisch Centrum Groningen, Postbus 30 001, 9700 RB Groningen
    Ned Tijdschr Geneeskd 150:2501-6. 2006
    ..After medical history, physical examination and an EMG, a short differential diagnosis based on the symptoms of myotonia was made...
  58. ncbi Modifications of gene expression in myotonic murine skeletal muscle are associated with abnormal expression of myogenic regulatory factors
    C Goblet
    Department of Molecular Biology, Pasteur Institute, Paris, France
    Dev Biol 170:262-73. 1995
    ..These observations suggest that specific myogenic factors may be linked to the expression of individual MyHC genes and that abnormal expression of some of the factors may be associated with myotonic muscle pathology...
  59. ncbi Electrophysiology and molecular pharmacology of muscle channelopathies
    K Jurkat-Rott
    Department of Physiology, Ulm University, Ulm, Germany
    Rev Neurol (Paris) 160:S43-8. 2004
    ..g. by designing drugs that specifically suppress the effects of malfunctioning channels...
  60. ncbi Intra- and interrater reliabilities of the Myotonometer when assessing the spastic condition of children with cerebral palsy
    Desiree D Aarrestad
    Physical Therapy Department, University of Montana, Missoula, MT 59812, USA
    J Child Neurol 19:894-901. 2004
    ..Novice users of the Myotonometer, with few exceptions, had high to very high intra- and interrater reliabilities for measurements of the biceps brachii and medial gastrocnemius muscles of children with spastic-type cerebral palsy...
  61. ncbi Dehydroepiandrosterone sulfate (DHEAS) therapy for myotonic dystrophy type 1 and myotonia
    Masakazu Sugino
    Intern Med 44:1213-4. 2005
  62. ncbi The effect of dehydroepiandrosterone sulfate (DHEAS) on myotonia: intracellular studies
    Hiroshi Nakazora
    Division of Neurology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
    Intern Med 44:1247-51. 2005
    In order to find some appropriate medicine to suppress myotonia without decreasing muscle strength experiments were performed on myotonic (mto) mice whose Cl channel does not develop due to stop codon and serves as an animal model of ..
  63. ncbi Neuromyotonia
    J Newsom-Davis
    Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK
    Rev Neurol (Paris) 160:S85-9. 2004
    ..These discoveries should aid diagnosis and offer new approaches to treatment...
  64. ncbi Treatment in myotonia and periodic paralysis
    G Meola
    Department of Neurology, University of Milan, Istituto Policlinico San Donato, Italy
    Rev Neurol (Paris) 160:S55-69. 2004
    ..or non-dystrophic myotonias (chloride, sodium, calcium and potassium channelopathies) are all characterized by myotonia and muscle weakness despite different pathophysiology involved in these disorders...
  65. ncbi Autosomal dominant monosymptomatic myotonia permanens
    Eskild Colding-Jørgensen
    Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark
    Neurology 67:153-5. 2006
    b>Myotonia permanens is associated with a G1306E mutation in the SCN4A gene. Two sporadic patients have been reported, but the clinical phenotype has not been fully characterized...
  66. ncbi A rare form of painful nondystrophic myotonia
    T Torbergsen
    Department of Neurology, Tromsø University Hospital, Tromsø, Norway
    Clin Neurophysiol 114:2347-54. 2003
    In this paper we report a painful nondystrophic myotonia which has not been previously described. Pain is a rare symptom in myotonia. We report a myotonic disorder in a 34-year-old woman and her 14-year-old daughter...
  67. ncbi Late-onset mitochondrial disorder with electromyographic evidence of myotonia
    Mathew L P Howse
    Department of Neurology, Middlesbrough General Hospital, Middlesbrough, Teeside, United Kingdom
    Muscle Nerve 28:757-9. 2003
    ..b>Myotonia has not previously been described in association with mitochondrial disease and this report extends the known ..
  68. ncbi Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies
    Y Y Vilin
    Department of Biology, Utah State University, Logan 84322, USA
    Cell Biochem Biophys 35:171-90. 2001
    ..inactivation is associated with several diseases of cell excitability, such as hyperkalemic periodic paralysis, myotonia, idiopathic ventricular fibrillation and long-QT syndrome...
  69. ncbi Respiratory compromise after MgSO4 therapy for preterm labor in a woman with myotonic dystrophy: a case report
    Val Catanzarite
    Department of Maternal Fetal Medicine, Sharp Mary Birch Hospital for Women and San Diego Perinatal Center, 92123, USA
    J Reprod Med 53:220-2. 2008
    ..MgSO4 is widely used for tocolysis. Serious complications are rare as long as dosing is carefully monitored. Adverse effects in muotonic dustrophy have not been previously described...
  70. ncbi Myotonic ADR-MDX mutant mice show less severe muscular dystrophy than MDX mice
    R Kramer
    Department of General Physiology, University of Ulm, Germany
    Neuromuscul Disord 8:542-50. 1998
    ..mutant mouse that combines two genetic defects: the dystrophin-deficiency of the MDX mouse and the Cl- channel myotonia of the arrested development of righting response (ADR) mouse...
  71. ncbi Expression of the potassium channel KV3.4 in mouse skeletal muscle parallels fiber type maturation and depends on excitation pattern
    D Vullhorst
    Developmental Biology Unit, University of Bielefeld, Germany
    FEBS Lett 421:259-62. 1998
    ..In denervated extensor digitorum longus, KV3.4 expression declines to perinatal levels. We conclude that KV3.4 expression in mouse skeletal muscle is regulated by the pattern of excitation...
  72. pmc Chloride conductance in mouse muscle is subject to post-transcriptional compensation of the functional Cl- channel 1 gene dosage
    M F Chen
    Developmental Biology Unit, University of Bielefeld, Germany
    J Physiol 504:75-81. 1997
    ..to less than 10% of that of wild-type, and this causes hyperexcitability, the salient feature of the disease myotonia. Potassium conductance (GK) values in myotonic mouse muscle fibres are lowered by about 60% compared with wild-..
  73. ncbi Immunohistological analyses of neutral glycosphingolipids and gangliosides in normal mouse skeletal muscle and in mice with neuromuscular diseases
    M Cacic
    Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, Croatia
    Glycoconj J 12:721-8. 1995
    ..Mice with neuromuscular diseases were the A2G-adr mouse mutant (a model for human recessive myotonia of Becker type), the BL6-wr mutant (a model for motor neuron disease) and the BL10-mdx mouse mutant (a model for ..
  74. pmc Myotonia and flaccid dysarthria in patients with adult onset myotonic dystrophy
    B J M de Swart
    Neuromuscular Centre Nijmegen, Institute of Neurology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands
    J Neurol Neurosurg Psychiatry 75:1480-2. 2004
    b>Myotonia and weakness are the most important components of dysarthric speech in myotonic dystrophy.
  75. ncbi [Syndromes of continuous muscular activity: report of a central case (stiff-man) and a peripheral case (neuromyotonia) associated with neuroborreliosis]
    I Requena
    Departamento de Medicina, Universidad de Santiago de Compostela, SERGAS
    Rev Neurol 23:129-33. 1995
    ..Both cases reacted favourably to medical treatment. In the first case botulinic toxin was used as a simultaneous treatment for focal pseudodystonia in one foot. Response was good...
  76. ncbi Nonsense and missense mutations in the muscular chloride channel gene Clc-1 of myotonic mice
    M Gronemeier
    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany
    J Biol Chem 269:5963-7. 1994
    ..Its functional defect leads to the disease myotonia. The ADR mouse (phenotype ADR, genotype adr/adr) is an animal model for human myotonias...
  77. ncbi Skeletal-muscle channelopathies: periodic paralysis and nondystrophic myotonias
    Aisling M Ryan
    MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
    Curr Opin Neurol 20:558-63. 2007
    ..To provide a current review of clinical phenotypes, genetics, molecular pathophysiology, and electro-diagnostic testing strategies of periodic paralysis and nondystrophic myotonias...
  78. pmc Mexiletine block of disease-associated mutations in S6 segments of the human skeletal muscle Na(+) channel
    M P Takahashi
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    J Physiol 537:701-14. 2001
    ..in the alpha-subunit of the adult skeletal muscle Na(+) channel (hSkM1) have been identified as a cause of myotonia or periodic paralysis...
  79. ncbi The skeletal muscle sodium and chloride channel diseases
    A J Hudson
    Department of Clinical Neurological Sciences, University Hospital, London, Ontario, Canada
    Brain 118:547-63. 1995
    ..the inactivation gate (ID3-4 loop) of the sodium channel tend to produce paramyotonia or pure, sometimes severe, myotonia and respond most favourably to the same medications (tocainide and mexiletine)...
  80. ncbi Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities
    H Seznec
    INSERM UR383, Hopital Necker Enfants Malades, Universite Rene Descartes Paris V, 149 161 Rue de Sèvres, 75743 Paris Cedex 15, France
    Hum Mol Genet 10:2717-26. 2001
    ..This multisystemic disorder includes myotonia, progressive weakness and wasting of skeletal muscle and extramuscular symptoms such as cataracts, testicular ..
  81. ncbi Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis
    Y Sugiura
    Department of Neurology, Fukushima Medical University School of Medicine, Fukushima, Japan
    Neurology 54:2179-81. 2000
    The authors report a Japanese family with dominantly inherited heat-induced myotonia and cold-induced paralysis with hypokalemia...
  82. ncbi The mouse Clc1/myotonia gene: ETn insertion, a variable AATC repeat, and PCR diagnosis of alleles
    V Schnülle
    Developmental Biology Unit, University of Bielefeld, Germany
    Mamm Genome 8:718-25. 1997
    ..Close to the 3' end of intron 12, a tetranucleotide repeat (AATC)n was found that is polymorphic between mouse species Mus musculus, M. molossinus, M. castaneus, and M. spretus, and can thus be used for chromosomal mapping studies...
  83. ncbi Role of innervation, excitability, and myogenic factors in the expression of the muscular chloride channel ClC-1. A study on normal and myotonic muscle
    R Klocke
    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany
    J Biol Chem 269:27635-9. 1994
    ..of the corresponding gene by mutations leads to hyperexcitability of muscle, the hallmark of the disease myotonia. In the mouse, there is very little ClC-1 mRNA in myotubes, and its concentration increases steeply during ..
  84. ncbi Subtractive cDNA cloning as a tool to analyse secondary effects of a muscle disease. Characterization of affected genes in the myotonic ADR mouse
    M Schleef
    University of Bielefeld, Developmental Biology Unit, Germany
    Neuromuscul Disord 4:205-17. 1994
    ..A cDNA derived from the 1100 nucleotide parvalbumin transcript was cloned and the sequence for the as yet unknown 3' extended trailer, generated by alternative polyadenylation, was determined...
  85. ncbi [Tributes to Macdonald Critchley and his achievements in neurolinguistics]
    Tsu Pei Hung
    College of Medicine, National Taiwan University, Taipei
    Acta Neurol Taiwan 17:127-31. 2008
    ..perseveration, anterior cerebral artery syndromes, indifference to pain, sleep disorders, movement disorders, and myotonia. He was very erudite and talented in linguistics; his interests were broad and eclectic...
  86. ncbi Disorders of membrane channels or channelopathies
    G G Celesia
    Department of Neurology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Avenue, IL, Maywood, USA
    Clin Neurophysiol 112:2-18. 2001
    ..To review the structure and function of membrane ion channels with special emphasis on inherited nervous system channel disorders or channelopathies...
  87. ncbi [Cardiac, respiratory and sleep disorders in patients with myotonic dystrophy]
    Marta Banach
    Pracownia EMG, Zakładu Neurofizjologii Klinicznej, Instytutu Psychiatrii i Neurologii w Warszawie
    Przegl Lek 66:1065-8. 2009
    ..Apart from myotonia and symptoms of skeletal muscle damage, the disease affects smooth muscles, heart muscle and the central nervous ..
  88. pmc Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families
    A Elbaz
    INSERM U134, Hopital de la Salpetriere, Paris
    Am J Hum Genet 56:374-80. 1995
    ..also comprises hyperkalemic periodic paralysis and paramyotonia congenita, both sodium-channel diseases, and myotonia congenita, a chloride-channel disorder...
  89. ncbi Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies
    G Meola
    Istituto Policlinico San Donato, Dipartimento di Neurologia, Cattedra di Clinica Neurologica, Universita di Milano, Ospedale di San Donato, Italy
    Eur J Histochem 47:17-28. 2003
    ..4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2...
  90. ncbi The nondystrophic myotonias
    Chad R Heatwole
    Department of Neurology, University of Rochester, Rochester, New York, USA
    Neurotherapeutics 4:238-51. 2007
    The nondystrophic myotonias are a heterogeneous set of rare diseases that demonstrate clinical myotonia, electrical myotonia, or both...
  91. ncbi [Myotonic dystrophy Curschmann-Steinert]
    E Papageorgiou
    Abteilung für Pathophysiologie des Sehens und Neuroophthalmologie, Universitäts Augenklinik Tübingen
    Klin Monbl Augenheilkd 224:70-5. 2007
    ..Characteristic clinical findings are muscular weakness and distal atrophy of the extremities, myotonia and myopathic facies. Ophthalmological symptoms may include cataract, ptosis and intraocular hypotension...
  92. ncbi [Thomsen myotonia congenita and strabismus: recording saccades in myotonic diseases]
    M Spire
    Service d Ophtalmologie, Hopital de la Croix Rousse, Lyon, France
    J Fr Ophtalmol 29:271-80. 2006
    Thomsen myotonia is an autosomal dominant, but not dystrophic myotonia. We report a family case associating congenital Thomsen's myotonia, strabismus, and ocular myopathy...
  93. ncbi Hypokalemic periodic paralysis in a patient with acquired growth hormone deficiency
    R Lanzi
    Endocrinology Unit, Department of Internal Medicine, San Raffaele Scientific Institute and Universita Vita Salute San Raffaele, Milan, Italy
    J Endocrinol Invest 30:341-5. 2007
    ....
  94. pmc Muscle channelopathies and electrophysiological approach
    Ajith Cherian
    Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, India
    Ann Indian Acad Neurol 11:20-7. 2008
    ..diseases are characterized by episodic failure of motor activity due to muscle weakness (paralysis) or stiffness (myotonia)...
  95. ncbi Maintaining constant voluntary force in generalized myotonia despite muscle membrane disturbances: insights from a high-density surface EMG study
    Gea Drost
    Department of Clinical Neurophysiology, Institute of Neurology, University Medical Centre Nijmegen, Amsterdam, The Netherlands
    J Clin Neurophysiol 21:114-23. 2004
    At medium and high force levels, patients with generalized myotonia (GM) cannot produce normal force because of a peculiar transient paresis...
  96. ncbi Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness
    Jose E Martinez-Rodriguez
    Neurology Service, Hospital Clinic i Provincial de Barcelona and Institut d lnvestigació Biomédica August Pi i Sunyer IDIBAPS, Barcelona, Spain
    Sleep 26:287-90. 2003
    Myotonic dystrophy type 1 is a multisystem disorder with myotonia, muscle weakness, cataracts, endocrine dysfunction, and intellectual impairment...
  97. ncbi Quantification of mobility impairment and self-assessment of stiffness in patients with myotonia congenita by the physiotherapist
    Elisabet Hammarén
    Neuromuscular Centre, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden
    Neuromuscul Disord 15:610-7. 2005
    ..and in three self-assessment scales, Visual Analogue Scale (VAS), Borg's Category-Ratio Scale (BorgCR10) and Myotonia Behaviour Scale (MBS) when quantifying myotonic stiffness and mobility impairment...
  98. ncbi Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy
    Eric L Logigian
    Neuromuscular Division, Department of Neurology, Box 673, 601 Elmwood Avenue, University of Rochester Medical Center, Rochester, New York 14642, USA
    Muscle Nerve 35:479-85. 2007
    To characterize and compare electrical myotonia in myotonic dystrophy type 1 (DM1) and type 2 (DM2), 16 patients with genetically confirmed DM1 and 17 patients with DM2 underwent standardized concentric needle electromyography of deltoid, ..
  99. ncbi Exercise test on the patients with normokalaemic periodic paralysis from a Chinese family with a mutation in the SCN4A gene
    Yu Feng
    Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
    Chin Med J (Engl) 121:1915-9. 2008
    ..some of patients with atypical normoKPP from those who suffer from other periodic paralysis and nondystrophic myotonia. So far, for normoKPP there are almost no ways to assist definite diagnosis besides genetic screening...
  100. ncbi Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia
    C Lorenz
    Center for Molecular Neurobiology ZMNH, Hamburg University, Germany
    Hum Mol Genet 3:941-6. 1994
    ..channel (CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's disease, GM) and autosomal dominant myotonia congenita (Thomsen's disease, MC)...
  101. ncbi ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence
    C Kubisch
    Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
    Hum Mol Genet 7:1753-60. 1998
    Mutations in the ClC-1 muscle chloride channel cause either recessive or dominant myotonia congenita...

Research Grants62

  1. Intravenous Protein Therapy for Myotonic Dystrophy Type 1
    Richard Weisbart; Fiscal Year: 2010
    ..the lack of DMPK activity does not fully account for the observed phenotype in DM1;including muscle wasting and myotonia, insulin resistance, testicular atrophy, cutaneous tumors cardiac arrhythmia and cognition defects (4- 8)...
  2. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2013
    ..lead to the synthesis of proteins with altered functionalities that cause genetically inherited disorders such as myotonia congenita, Bartter's syndrome, Dent's disease, osteopetrosis and epilepsy...
  3. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2013
    ..affecting skeletal muscle contraction (hyperkalemic periodic paralysis, paramyotonia congenita, K+-aggravated myotonia), cardiac excitability (congenital long QT syndrome, idiopathic ventricular fibrillation, familial conduction ..
  4. Molecular mechanisms of Myotonic Dystrophy 1
    Lubov T Timchenko; Fiscal Year: 2012
    ..Myotonic Dystrophy type 1 (DM1) primarily affects skeletal muscle causing muscle wasting, weakness and myotonia. The most severe, congenital form of DM1 (CDM1) affects children delaying maturation of myofibers...
  5. Antisense oligonucleotide treatment for myotonic dystrophy
    Charles A Thornton; Fiscal Year: 2013
    ..knockdown of CUG(R)"''transcripts in muscle, reversal of RNA splicing derangements, and rescue of myotonia in transgenic mice...
  6. Phase II Therapeutic Trial of Mexiletine
    Richard J Barohn; Fiscal Year: 2010
    ..Mexiletine also improves functional behavior in a mouse model of severe recessive myotonia congenita...
  7. Chemical biology of voltage-gated sodium and potassium channels
    Christopher A Ahern; Fiscal Year: 2013
    ..health is highlighted by the facts that: inherited or acquired defects in NaV or Kv channels cause epilepsy, myotonia, erythromelalgia and cardiac arrhythmias;mutations that lead to changes in the gating kinetics or expression of K+..
  8. MOLECULAR MECHANISMS OF THE MYOTONIC DYSTROPHY MUTATION
    MANI SUBRAMANIAM MAHADEVAN; Fiscal Year: 2013
    ..we found that mice overexpressing a normal DMPK 3'UTR mRNA reproduced cardinal features of DM including myotonia, cardiac conduction abnormalities, DM histopathology and RNA splicing defects in the absence of detectable ..
  9. Molecular Physiology of Myotonia and Periodic Paralysis
    Stephen C Cannon; Fiscal Year: 2013
    ..b>Myotonia is a disorder of enhanced excitability wherein a single stimulus elicits a high- frequency burst of action ..
  10. Development of RNA interference for treatment of myotonic dystrophy in the HSALR
    Joel R Chamberlain; Fiscal Year: 2010
    ..common form of muscular dystrophy in adults, and is characterized by a wide range of clinical features including myotonia (muscle hyperexcitability), progressive myopathy, cardiac conduction defects, hyperinsulinemia, and ..
  11. Molecular Physiology of CLC Chloride Channels
    Tsung Yu Chen; Fiscal Year: 2012
    ..important because mutations that disrupt the common- gating of CLC-1 are known to cause the dominant form of myotonia. In this application we will combine electrophysiological and fluorescence imaging approaches to study how ATP ..
  12. RNA-mediated Mechanisms in the Myotonic Dystrophies
    Charles A Thornton; Fiscal Year: 2011
    ..It is clear that spliceopathy can explain certain aspects of the phenotype, such as, myotonia, but the range of genes that are affected, and how the spliceopathy relates to the full spectrum of clinical ..
  13. Pathogenesis of Myopathy in Models of Myotonic Dystrophy
    Charles Thornton; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Myotonic dystrophy type 1 [DM1] leads to maldevelopment, myotonia, and wasting of skeletal muscle. DM1 is caused by an unstable CTG repeat expansion in the 3'untranslated region of DMPK...
  14. High Resolution Structural Dyanmics of K Channels
    EDUARDO A PEROZO; Fiscal Year: 2013
    ..K+ channel dysfunction may lead to uncontrolled periods of electrical hyperexcytability, like epileptic episodes, myotonia and cardiac arrhythmia...
  15. Targeting a Toxic RNA with Small Molecules
    JOHN ANDREW BERGLUND; Fiscal Year: 2013
    ..by repeat nucleotide expansions, specifically CUG and CCUG expansions in the non-coding regions of the dystrophia myotonia protein kinase gene (DMPK) and the Zn finger 9 gene (ZNF9), respectively...
  16. Mechanisms of Gating in Voltage-dependent Sodium Channels
    Baron Chanda; Fiscal Year: 2013
    ..genes have been linked to disease conditions such as congenital long QT syndrome, generalized epilepsy and muscle myotonia. Despite much progress in understanding the role of sodium channels in the human body, there remains a ..
  17. Myotonic Dystrophy Type 2
    Lubov T Timchenko; Fiscal Year: 2013
    ..multisystemic disease, that primarily affects skeletal muscle causing skeletal muscle loss, muscle weakness and myotonia. DM2 is caused by expansion of CCTG repeats in the intron 1 of ZNF9 gene...
  18. Mechanism and function of a novel purinergic signaling cascade in skeletal muscle
    ANDREW ALVIN VOSS; Fiscal Year: 2013
    ..muscle that underlie exercise-induced fatigue, changes during disuse, and the symptoms of diseases such as myotonia congenita are not fully understood...
  19. Nervous System Channelopathies: Pathogenesis and Treatment
    Robert C Griggs; Fiscal Year: 2010
    ..Treatment, focusing on the prototypic episodic disorders periodic paralysis, episodic ataxia and nondystrophic myotonia. It exploits the strengths of 10 collaborating centers in 4 countries to link molecular scientists with clinical ..
  20. MOLECULAR MECHANISMS OF MYOTONIC DYSTROPHY
    JOHN A BERGLUND; Fiscal Year: 2010
    ..dystrophy (DM) is caused by nucleotide expansions of CUG and CCUG in the non-coding regions of the dystrophia myotonia protein kinase gene (DMPK) and the Zn finger 9 gene (ZNF9) respectively...
  21. Dynamic Calmodulin Regulation of Na Channels
    David T Yue; Fiscal Year: 2013
    ..biological and clinical impact of NaV channels, which include mentation (epilepsy), muscle contraction (myotonia and arrhythmias), and sensation (neuropathic pain)...
  22. Phase 2 Study of Mexiletine for the Treatment of Myotonic Dystrophy
    Richard T Moxley; Fiscal Year: 2013
    ..Distal muscle weakness in the arms and legs, along with facial weakness and grip myotonia may occur along with impaired ambulation, unsteadiness on arising from a chair, difficulty with fine finger ..
  23. Molecular Mechanisms Underlying DM1
    Sita Reddy; Fiscal Year: 2010
    ..Importantly, loss of Mbnl function has been shown to result in myotonia and central nuclei. However all features of DM1 skeletal muscle disease are not observed in Mbnl knockout mice...
  24. MOLECULAR PHYSIOLOGY OF HYPERKALEMIC PERIODIC PARALYSIS
    Lawrence Hayward; Fiscal Year: 2001
    Hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PMC), and sodium channel myotonia (SCM), are dominantly inherited myotonic disorders caused by missense mutations in the skeletal muscle sodium (Na) channel...
  25. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2009
    ..affecting skeletal muscle contraction (hyperkalemic periodic paralysis, paramyotonia congenita, K+-aggravated myotonia), cardiac excitability (congenital long QT syndrome, idiopathic ventricular fibrillation, familial conduction ..
  26. MECHANISM OF MIS-SPLICING IN MYOTONIC DYSTROPHY 1
    MUGE KUYUMCU MARTINEZ; Fiscal Year: 2007
    ..The functional consequences of mis-splicing of CIC-1 and IR directly correlate with myotonia and insulin resistance, respectively, observed in DM1...
  27. SODIUM CHANNEL GATING IN MODELS OF MYOTONIA
    Robert Ruff; Fiscal Year: 1991
    ..First, that sodium currents are increased by treatments which produce myotonia in rat skeletal muscle...
  28. STRUCTURE/FUNCTION STUDY OF A VOLTAGE GATED K CHANNEL
    Rolf Joho; Fiscal Year: 2000
    ..human neuromuscular disorders are ion channel diseases: Hyperkalemic periodic paralysis, paramyotonia congenita, myotonia, congenita, episodic ataxia, and some forms of cardiac arrhythmias, like long QT syndromes...
  29. MOLECULAR MECHANISMS IN SYNAPTIC VESICLE RECYCLING
    Mani Ramaswami; Fiscal Year: 2001
    ..mutations in a similar voltage-gated sodium channel of mammalian muscle result in periodic paralysis or a form of myotonia congenita in humans...
  30. PLAN FOR A TRIAL OF DHEAS IN MYOTONIC DYSTROPHY
    Charles Thornton; Fiscal Year: 2000
    ..improves or even slows the progressive muscle wasting and weakness that occur in myotonic dystrophy (dystrophica myotonia, DM), the most common inherited muscle disease in adults...
  31. Mechanisms of decay of toxic CUGn RNA in DM1 patients
    Lubov Timchenko; Fiscal Year: 2009
    ..that the accumulation of multiple copies of short CUG repeats of normal size in mice produced DM1-like phenotype (myotonia, muscular dystrophy and cardiac conduction defects), while mice with low number of copies of long CUG repeats ..
  32. ELECTROPHYSIOLOGY AND PHARMACOLOGY OF MYOTONIC MUSCLE
    SHIRLEY BRYANT; Fiscal Year: 1990
    The objective of this renewal application is to continue to investigate membrane mechanisms that underlie myotonia, a syndrome characterized by abnormal excitability leading to prolonged repetitive discharge of action potentials and ..
  33. Investigating mechanisms of skeletal muscle degeneration in Myotonic Dystrophy
    James P Orengo; Fiscal Year: 2010
    ..Although many symptoms in DM, such as myotonia and insulin resistance, are explained by particular misregulated splicing events, the mechanism by which skeletal ..
  34. Mechanisms of CIC-Type Chloride Channels Function
    JAMES MELVIN; Fiscal Year: 2005
    ..lead to either impaired transepithelial ion transport in Bartter's syndrome, to increased muscle excitability in myotonia congenita, to reduced endosomal acidification and endocytosis in Dent's disease, or to impaired extracellular ..
  35. CLONING/CHARACTERIZATING A MYOTONIC DYSTROPHY LOCUS
    LAURA RANUM; Fiscal Year: 2004
    ..Affected members have the characteristic features of DM (myotonia, proximal and distal limb weakness, frontal balding, cataracts, and cardiac arrhythmias) but do not have the ..
  36. Molecular Genetic Characterization of Myotonic Dystrophy
    Ralf Krahe; Fiscal Year: 2005
    ..group of neuromuscular disorders, characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multi-system involvement...
  37. DM2: Murine and cell Culture Models of CCUG RNA toxicity
    LAURA RANUM; Fiscal Year: 2007
    ..of myotonic dystrophy that causes a strikingly similar constellation of clinical features in humans including myotonia, myopathy, iridescent cataracts, cardiac arrhythmias, and the specific set of serological changes characteristic ..
  38. Molecular basis of ion selectivity in the prokaryotic voltage-gated Na+ channel
    MEHABAW DEREBE; Fiscal Year: 2009
    ..Some of these diseases are epilepsy, long QT syndrome, periodic paralysis, myotonia, etc...
  39. HEREDITARY DEFECTS IN HUMAN CHLORIDE CHANNELS
    ALFRED GEORGE; Fiscal Year: 2001
    ..skeletal muscle have been shown by a number of groups, including the applicant's, to result in inherited forms of myotonia congenita...
  40. Probing conformational changes in CLC chloride transport proteins using 19F NMR
    SHELLEY ELVINGTON; Fiscal Year: 2009
    ..Defects in CLC chloride transport proteins can lead to a variety of human diseases, including epilepsy, myotonia, Barrier's syndrome, osteoporosis, and Dent's disease...
  41. ABERRANT RNA PROCESSING IN HUMAN DEVELOPMENT
    Adil Shamoo; Fiscal Year: 2002
    ..expansion of CUG repeats in an untranslated region of the myotonin kinase gene and results in symptoms from mild myotonia to severe retardation at birth. DM is an unfortunately common disease (1 in 8000 births)...
  42. Channelopathy Based Investigation of Domain-Specific Functions in Sodium Channels
    James Groome; Fiscal Year: 2009
    ..PI to study novel channel functions, and novel mechanisms of channel dysfunction in ion channel diseases such as myotonia and epilepsy...
  43. Transmitter Repletion: Key to Phrenic-Diaphragm Function
    Erik van Lunteren; Fiscal Year: 2005
    ..These studies may lead to novel therapeutic approaches to respiratory muscle impairment and resulting hypercapnic respiratory failure for conditions which produce neuromuscular junction dysfunction. ..
  44. Ginkgo Biloba: Antidepressant-Induced Sexual Dysfunction
    Cindy Meston; Fiscal Year: 2003
    ..If effective, GBE could play a significant adjunctive role in the treatment of clinical depression and other psychological disorders commonly treated with antidepressant medications. ..
  45. MRI, MIT, and MRS of MPS VII and Krabbe Disease
    Charles Vite; Fiscal Year: 2003
    ..x0a; ..
  46. MOLECULAR BASIS OF LIGAND/SODIUM CHANNEL INTERACTIONS
    GING WANG; Fiscal Year: 2002
    ....
  47. THERAPEUTIC NA+ CHANNEL BLOCKERS: RECEPTOR & DRUG DESIGN
    GING WANG; Fiscal Year: 2007
    ..Such drugs, either taken orally or injected locally, may be beneficial for patients with chronic and intractable cancer pain. ..
  48. Second Ataxia investigator Meeting
    John Day; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  49. Effects of Early Abuse on Adult Intimate Relationships
    Cindy M Meston; Fiscal Year: 2010
    ..The findings from this investigation will have implications for understanding both the psychological and physiological mechanisms that link CA with detrimental intimacy/relational factors in adulthood. ..
  50. Molecular Physiology of Neuromusclar Diseases
    Stephen Cannon; Fiscal Year: 2007
    ..b>Myotonia is a disorder of enhanced excitability wherein a single stimulus elicits a burst of action potentials that ..
  51. APPLICATION OF NOVEL OPTICAL METHODS TO CELL DYNAMICS
    Alan Verkman; Fiscal Year: 2001
    ..These studies will address the hypothesis that the membrane skeleton of these cells is a mobile, dynamic structure. ..
  52. STRUCTURE/FUNCTION OF THE HUMAN 2P DOMAIN CHANNEL HTPKC1
    Detlef Bockenhauer; Fiscal Year: 2004
    ..The Departments of Physiology and Pharmacology at Yale is staffed with an internationally recognized cadre of ion channel researchers. ..
  53. APPLICATION OF NOVEL OPTICAL METHODS TO CELL DYNAMICS
    Alan Verkman; Fiscal Year: 2006
    ..abstract_text> ..
  54. Role of SOD Instability in ALS Motor Neuron Toxicity
    Lawrence Hayward; Fiscal Year: 2006
    ..Future results from Aims 1 and 2 may favor alternative hypotheses of mutant SOD1 toxicity to test in these cellular models and may suggest new therapeutic approaches to evaluate in ALS mice. ..
  55. PHYSIOLOGY AND MOLECULAR BIOLOGY OF LUNG WATER TRANSPORT
    Alan Verkman; Fiscal Year: 2007
    ..abstract_text> ..
  56. Inducible Transgenic Mouse Model of RNA Toxicity
    MANI MAHADEVAN; Fiscal Year: 2009
    ..All DM patients have endured exposure to the toxic RNA from birth and thus a model such as this one will be able to provide valuable and relevant insight into this therapeutic strategy. ..
  57. Role of airway submucosal glands in CF lung disease
    Alan S Verkman; Fiscal Year: 2010
    ..The data will provide a rigorous scientific rationale for use of small-molecules in CF therapy, and establish widely useful assays to prioritize small molecules for clinical development. ..
  58. Pathogenic Mechanism of Spinocerebellar Ataxia Type 10
    Tetsuo Ashizawa; Fiscal Year: 2009
    ..Establishing the mechanism in SCA10 will fill the current gap of knowledge and facilitate the development of rational therapy. ..