Robert Dirksen

Summary

Affiliation: University of Rochester
Country: USA

Publications

  1. ncbi request reprint Suramin interacts with the calmodulin binding site on the ryanodine receptor, RYR1
    Rao V L Papineni
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 277:49167-74. 2002
  2. ncbi request reprint Rapamycin and FK506 reduce skeletal muscle voltage sensor expression and function
    Guillermo Avila
    Department of Biochemistry, CINVESTAV IPN, AP 14 740 Mexico City, DF 07000, Mexico
    Cell Calcium 38:35-44. 2005
  3. pmc The pore region of the skeletal muscle ryanodine receptor is a primary locus for excitation-contraction uncoupling in central core disease
    Guillermo Avila
    Department of Biochemistry, Cinvestav I P N, Zacatenco 07360, Mexico City, Mexico
    J Gen Physiol 121:277-86. 2003
  4. pmc Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling
    Sanjeewa A Goonasekera
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 130:365-78. 2007
  5. pmc Calmodulin binding to the 3614-3643 region of RyR1 is not essential for excitation-contraction coupling in skeletal myotubes
    Kristen M S O'Connell
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    J Gen Physiol 120:337-47. 2002
  6. pmc Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum
    Ryan E Loy
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 137:43-57. 2011
  7. pmc Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death
    Viktor Yarotskyy
    Department of Physiology and Pharmacology, University of Rochester Medical Center, Rochester, New York, United States of America
    PLoS ONE 8:e77633. 2013
  8. pmc Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy
    Ryan E Loy
    Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, United States of America
    PLoS ONE 7:e49757. 2012
  9. pmc Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy
    John D Lueck
    Department of Physiology and Pharmacology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 129:79-94. 2007
  10. pmc Functional impact of the ryanodine receptor on the skeletal muscle L-type Ca(2+) channel
    G Avila
    Department of Pharmacology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Gen Physiol 115:467-80. 2000

Research Grants

  1. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert T Dirksen; Fiscal Year: 2010
  2. Molecular Mechanism and Functional Role of SOCE in Skeletal Muscle
    Robert T Dirksen; Fiscal Year: 2010
  3. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2002
  4. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2009
  5. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2007
  6. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2006
  7. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2005
  8. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2004
  9. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2003

Collaborators

Detail Information

Publications46

  1. ncbi request reprint Suramin interacts with the calmodulin binding site on the ryanodine receptor, RYR1
    Rao V L Papineni
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 277:49167-74. 2002
    ....
  2. ncbi request reprint Rapamycin and FK506 reduce skeletal muscle voltage sensor expression and function
    Guillermo Avila
    Department of Biochemistry, CINVESTAV IPN, AP 14 740 Mexico City, DF 07000, Mexico
    Cell Calcium 38:35-44. 2005
    ..e. the maximal rate of Ca2+ release per unit gating charge)...
  3. pmc The pore region of the skeletal muscle ryanodine receptor is a primary locus for excitation-contraction uncoupling in central core disease
    Guillermo Avila
    Department of Biochemistry, Cinvestav I P N, Zacatenco 07360, Mexico City, Mexico
    J Gen Physiol 121:277-86. 2003
    ..These data demonstrate that CCD mutations in exon 102 disrupt release channel permeation to Ca2+ during EC coupling and that this region represents a primary molecular locus for EC uncoupling in CCD...
  4. pmc Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling
    Sanjeewa A Goonasekera
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 130:365-78. 2007
    ..These findings demonstrate that junctin and triadin bind to different sites on RyR1 and that triadin plays an important role in ensuring rapid Ca(2+) release during excitation-contraction coupling in skeletal muscle...
  5. pmc Calmodulin binding to the 3614-3643 region of RyR1 is not essential for excitation-contraction coupling in skeletal myotubes
    Kristen M S O'Connell
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    J Gen Physiol 120:337-47. 2002
    ..The results indicate that CaM binding to the 3614-3643 region of RyR1 is not essential for voltage sensor activation of RyR1...
  6. pmc Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum
    Ryan E Loy
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 137:43-57. 2011
    ....
  7. pmc Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death
    Viktor Yarotskyy
    Department of Physiology and Pharmacology, University of Rochester Medical Center, Rochester, New York, United States of America
    PLoS ONE 8:e77633. 2013
    ....
  8. pmc Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy
    Ryan E Loy
    Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, United States of America
    PLoS ONE 7:e49757. 2012
    ..As determined by quantitative real time PCR, the degree of functional rescue in YS/+ and IT/+ mice correlated well with the relative increase in fractional WT allele expression...
  9. pmc Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy
    John D Lueck
    Department of Physiology and Pharmacology, University of Rochester, Rochester, NY 14642, USA
    J Gen Physiol 129:79-94. 2007
    ....
  10. pmc Functional impact of the ryanodine receptor on the skeletal muscle L-type Ca(2+) channel
    G Avila
    Department of Pharmacology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Gen Physiol 115:467-80. 2000
    ....
  11. pmc Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor
    G Avila
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    J Gen Physiol 118:277-90. 2001
    ..Two fundamentally distinct cellular mechanisms (leaky channels and EC uncoupling) are proposed to explain how altered release channel function caused by different mutations in RyR1 could result in muscle weakness in CCD...
  12. ncbi request reprint Bi-directional coupling between dihydropyridine receptors and ryanodine receptors
    Robert T Dirksen
    University of Rochester School of Medicine and Dentistry, Rochester, NY 14534, USA
    Front Biosci 7:d659-70. 2002
    ..This review will focus on evaluating the nature and molecular determinants of these coupling mechanisms, as well as the extent to which excitable cell function is influenced by bi-directional DHPR/RyR calcium signaling...
  13. pmc Sarcoplasmic reticulum-mitochondrial through-space coupling in skeletal muscle
    Robert T Dirksen
    Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Appl Physiol Nutr Metab 34:389-95. 2009
    ..This review will consider the degree to which this structural link enables privileged or microdomain communication between the SR and mitochondria in skeletal muscle...
  14. pmc Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle
    Robert T Dirksen
    Department of Pharmacology and Physiology, University of Rochester, NY 14642, USA
    J Physiol 587:3139-47. 2009
    ..Finally, potential physiological roles for SOCE and ECCE in skeletal muscle development and function, as well as other currently unanswered questions and controversies in the field are also considered...
  15. ncbi request reprint Altered ryanodine receptor function in central core disease: leaky or uncoupled Ca(2+) release channels?
    Robert T Dirksen
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Trends Cardiovasc Med 12:189-97. 2002
    ..These observations cannot be explained by the leaky-channel hypothesis and indicate that muscle weakness in some forms of CCD arises from an alternate and completely unexpected mechanism, termed "excitation-contraction uncoupling."..
  16. ncbi request reprint Reactive oxygen/nitrogen species and the aged brain: radical impact of ion channel function
    Robert T Dirksen
    Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rm 4 6423, Box 711, Rochester, NY 14642, USA
    Neurobiol Aging 23:837-9; discussion 841-2. 2002
  17. pmc Sarcoplasmic reticulum-mitochondrial symbiosis: bidirectional signaling in skeletal muscle
    Ann E Rossi
    Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Exerc Sport Sci Rev 37:29-35. 2009
    ..Retrograde signaling involves mitochondrial inhibition of local SR Ca release by controlling the redox environment of the Ca release unit...
  18. ncbi request reprint Two central core disease (CCD) deletions in the C-terminal region of RYR1 alter muscle excitation-contraction (EC) coupling by distinct mechanisms
    Alla D Lyfenko
    Department of Physiology and Pharmacology, University of Rochester, Rochester, New York 14642, USA
    Hum Mutat 28:61-8. 2007
    ..Val4927_Ile4928del deletion reduces Ca(2+) release by disrupting Ca(2+) gating and eliminating Ca(2+) permeation through the open channel...
  19. ncbi request reprint Reconstitution of local Ca2+ signaling between cardiac L-type Ca2+ channels and ryanodine receptors: insights into regulation by FKBP12.6
    Sanjeewa A Goonasekera
    Dept of Pharmacology and Physiology, Univ of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA
    Am J Physiol Cell Physiol 289:C1476-84. 2005
    ..6 expression. Thus a negative charge at S2808 does not alter in situ regulation of RyR2 by FKBP12.6...
  20. pmc Distinct effects on Ca2+ handling caused by malignant hyperthermia and central core disease mutations in RyR1
    Robert T Dirksen
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York, USA
    Biophys J 87:3193-204. 2004
    ....
  21. pmc Epac and phospholipase Cepsilon regulate Ca2+ release in the heart by activation of protein kinase Cepsilon and calcium-calmodulin kinase II
    Emily A Oestreich
    Department of Pharmacology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 284:1514-22. 2009
    ....
  22. ncbi request reprint Dynamic alterations in myoplasmic Ca2+ in malignant hyperthermia and central core disease
    Alla D Lyfenko
    Department of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Biochem Biophys Res Commun 322:1256-66. 2004
    ..This review focuses on recent advances in determining the impact of MH and CCD mutations in RyR1 on muscle Ca2+ signaling and how these effects contribute to disease-specific aspects of these disorders...
  23. ncbi request reprint Sarcoplasmic reticulum: the dynamic calcium governor of muscle
    Ann E Rossi
    Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA
    Muscle Nerve 33:715-31. 2006
    ..g., malignant hyperthermia, central core disease, and Brody disease) can result from subtle alterations in the activity of several key components of the SR calcium-regulatory machinery...
  24. pmc Mitochondrial ryanodine receptors and other mitochondrial Ca2+ permeable channels
    Shin Young Ryu
    Department of Pharmacology and Physiology, and Mitochondrial Research Innovation Group, University of Rochester Medical Center, Rochester, NY 14642, USA
    FEBS Lett 584:1948-55. 2010
    ..Here, we discuss recent progresses in the biophysical and electrophysiological characterization of several distinct mitochondrial Ca(2+) channels...
  25. ncbi request reprint Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation
    Conrad C Alano
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA
    J Neurochem 80:531-8. 2002
    ..The presented results indicate that MPT can be detected in living neurons using fluorescent Ca2+ indicators, which would allow the study of the physiological role of MPT in cell death...
  26. pmc Differential dependence of store-operated and excitation-coupled Ca2+ entry in skeletal muscle on STIM1 and Orai1
    Alla D Lyfenko
    Department of Physiology and Pharmacology, University of Rochester, Rochester, NY 14642, USA
    J Physiol 586:4815-24. 2008
    ..These results are the first to demonstrate that SOCE in skeletal muscle requires both STIM1 and Orai1 and that SOCE and ECCE represent two distinct molecular entities...
  27. pmc ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes
    Xiangrong He
    Center for Cardiovascular Research, University of Rochester Medical Center, Rochester, New York 14642, USA
    Am J Pathol 163:243-51. 2003
    ..We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure...
  28. ncbi request reprint Epac-mediated activation of phospholipase C(epsilon) plays a critical role in beta-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac myocytes
    Emily A Oestreich
    Department of Pharmacology, University of Rochester School of Medicine, Rochester, New York 14642, USA
    J Biol Chem 282:5488-95. 2007
    ..These data define a novel endogenous PKA-independent betaAR-signaling pathway through cAMP-dependent Epac activation, Rap, and PLC(epsilon) that enhances intracellular Ca(2+) release in cardiac myocytes...
  29. ncbi request reprint Type 1 ryanodine receptor in cardiac mitochondria: transducer of excitation-metabolism coupling
    Gisela Beutner
    Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, NY 14642, USA
    Biochim Biophys Acta 1717:1-10. 2005
    ..Thus, the mRyR functions as a transducer for excitation-metabolism coupling...
  30. ncbi request reprint Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and inhibits cardiac hypertrophy
    Huan Wang
    Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, NY 14642, USA
    Circ Res 97:1305-13. 2005
    ....
  31. pmc Differential impact of mitochondrial positioning on mitochondrial Ca(2+) uptake and Ca(2+) spark suppression in skeletal muscle
    Ann E Rossi
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Am J Physiol Cell Physiol 301:C1128-39. 2011
    ..95) to an increase in mitochondrion-CRU pairing. Together, these results indicate that mitochondrion-CRU association promotes Ca(2+) spark suppression but does not significantly impact mitochondrial Ca(2+) uptake...
  32. pmc Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease
    Lan Wei
    University of Rochester Medical Center, Department of Pharmacology and Physiology, Rochester, NY 14642, USA
    FASEB J 25:3068-78. 2011
    ..Together, these results demonstrate that mSOF activity is a highly sensitive biomarker of mitochondrial respiration and the cellular metabolic state of muscle during physiological activity and pathological oxidative stress..
  33. ncbi request reprint Chloride channelopathy in myotonic dystrophy resulting from loss of posttranscriptional regulation for CLCN1
    John D Lueck
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Am J Physiol Cell Physiol 292:C1291-7. 2007
    ....
  34. ncbi request reprint Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse
    Mihail G Chelu
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
    FASEB J 20:329-30. 2006
    ..We conclude that the heterozygous expression of the Y522S mutation confers susceptibility to both heat- and anesthetic-induced MH responses...
  35. ncbi request reprint Functional analysis of the R1086H malignant hyperthermia mutation in the DHPR reveals an unexpected influence of the III-IV loop on skeletal muscle EC coupling
    Regina G Weiss
    Department of Biochemical Pharmacology, Innsbruck Medical Univ, Peter Mayr Strasse 1, A 6020 Innsbruck, Austria
    Am J Physiol Cell Physiol 287:C1094-102. 2004
    ..These results indicate that the R1086H MH mutation in alpha(1S) enhances RyR1 sensitivity to activation by both endogenous (voltage sensor) and exogenous (caffeine) activators...
  36. ncbi request reprint Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1
    Takashi Kimura
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601, Australia
    Hum Mol Genet 14:2189-200. 2005
    ..We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle...
  37. ncbi request reprint Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1
    Paula Aracena-Parks
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 281:40354-68. 2006
    ..In summary, we have identified a discrete subset of cysteines that are likely to be involved in the functional response of RyR1 to different redox modifications (S-nitrosylation, S-glutathionylation, and oxidation to disulfides)...
  38. pmc An Ryr1I4895T mutation abolishes Ca2+ release channel function and delays development in homozygous offspring of a mutant mouse line
    Elena Zvaritch
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 104:18537-42. 2007
    ....
  39. ncbi request reprint FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes
    Guillermo Avila
    Department of Biochemistry, CINVESTAV IPN, AP 14 740, Mexico City, DF 07000, Mexico
    J Biol Chem 278:22600-8. 2003
    ..These data demonstrate that FKBP12 binding to RyR1 enhances the gain of skeletal muscle EC coupling...
  40. pmc Superoxide flashes in single mitochondria
    Wang Wang
    Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Cell 134:279-90. 2008
    ..We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases...
  41. pmc Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:12179-84. 2006
    ..Our results suggest that the R176Q mutation in RyR2 predisposes the heart to catecholamine-induced oscillatory calcium-release events that trigger a calcium-dependent ventricular arrhythmia...
  42. pmc A variably spliced region in the type 1 ryanodine receptor may participate in an inter-domain interaction
    Takashi Kimura
    Division of Molecular Bioscience, JCSMR John Curtin School of Medical Research, Australian National University, P O Box 334, Canberra, ACT 2601, Australia
    Biochem J 401:317-24. 2007
    ....
  43. ncbi request reprint Role of the sequence surrounding predicted transmembrane helix M4 in membrane association and function of the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor isoform 1)
    Guo Guang Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 279:37566-74. 2004
    ..Thus, this region may act as a negative regulatory module that increases the energy barrier for Ca(2+) release channel opening...
  44. pmc Potentiated L-type Ca2+ channels rectify
    Valerie Leuranguer
    Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA
    J Gen Physiol 121:541-50. 2003
    ..These results can be explained by postulating that potentiation exposes a binding site in the pore to which an intracellular blocking particle can bind and produce inward rectification of the potentiated channels...

Research Grants11

  1. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert T Dirksen; Fiscal Year: 2010
    ....
  2. Molecular Mechanism and Functional Role of SOCE in Skeletal Muscle
    Robert T Dirksen; Fiscal Year: 2010
    ..Thus, discoveries resulting from this proposal will provide promise for the development of novel approaches, treatments, and diagnostics for a wide range of diseases in Ca2+ signaling. ..
  3. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2002
    ..abstract_text> ..
  4. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2009
    ....
  5. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2007
    ....
  6. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2006
    ..abstract_text> ..
  7. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2005
    ..abstract_text> ..
  8. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2004
    ..abstract_text> ..
  9. CONTROL OF CALCIUM MOVEMENTS IN MUSCLE
    Robert Dirksen; Fiscal Year: 2003
    ..abstract_text> ..