l type calcium channels

Summary

Summary: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.

Top Publications

  1. pmc Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases
    Brian S Finlin
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536 0298, USA
    Proc Natl Acad Sci U S A 100:14469-74. 2003
  2. ncbi Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism
    Igor Splawski
    Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cell 119:19-31. 2004
  3. ncbi 'Rejuvenation' protects neurons in mouse models of Parkinson's disease
    C Savio Chan
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Nature 447:1081-6. 2007
  4. ncbi Preassociation of calmodulin with voltage-gated Ca(2+) channels revealed by FRET in single living cells
    M G Erickson
    Department of Biomedical Engineering, Calcium Signals Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 31:973-85. 2001
  5. ncbi Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway
    R E Dolmetsch
    Division of Neuroscience, Children's Hospital and Department of Neurobiology, Harvard Medical School, Enders Pediatric Research Laboratories, Room 260, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 294:333-9. 2001
  6. pmc The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor
    Natalia Gomez-Ospina
    Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA
    Cell 127:591-606. 2006
  7. ncbi Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines
    W Xu
    Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA
    J Neurosci 21:5944-51. 2001
  8. ncbi Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels
    G S Pitt
    Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305, USA
    J Biol Chem 276:30794-802. 2001
  9. ncbi Unified mechanisms of Ca2+ regulation across the Ca2+ channel family
    Haoya Liang
    Ca2 Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Neuron 39:951-60. 2003
  10. ncbi Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels
    J Platzer
    Institut fur Biochemische Pharmakologie, Innsbruck, Austria
    Cell 102:89-97. 2000

Detail Information

Publications301 found, 100 shown here

  1. pmc Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases
    Brian S Finlin
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536 0298, USA
    Proc Natl Acad Sci U S A 100:14469-74. 2003
    ..Thus, the RGK GTPase family may provide a mechanism for achieving cross talk between Ras-related GTPases and electrical signaling pathways...
  2. ncbi Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism
    Igor Splawski
    Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cell 119:19-31. 2004
    ..These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism...
  3. ncbi 'Rejuvenation' protects neurons in mouse models of Parkinson's disease
    C Savio Chan
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Nature 447:1081-6. 2007
    ..Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease...
  4. ncbi Preassociation of calmodulin with voltage-gated Ca(2+) channels revealed by FRET in single living cells
    M G Erickson
    Department of Biomedical Engineering, Calcium Signals Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 31:973-85. 2001
    ..These results now definitively demonstrate channel-CaM preassociation in resting cells and underscore the potential of three-cube FRET for probing protein-protein interactions...
  5. ncbi Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway
    R E Dolmetsch
    Division of Neuroscience, Children's Hospital and Department of Neurobiology, Harvard Medical School, Enders Pediatric Research Laboratories, Room 260, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 294:333-9. 2001
    ..CaM functions as a local Ca2+ sensor at the mouth of the LTC that activates the MAPK pathway and leads to the stimulation of genes that are essential for neuronal survival and plasticity...
  6. pmc The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor
    Natalia Gomez-Ospina
    Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA
    Cell 127:591-606. 2006
    ..These findings provide evidence that voltage-gated calcium channels can directly activate transcription and suggest a mechanism linking voltage-gated channels to the function and differentiation of excitable cells...
  7. ncbi Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines
    W Xu
    Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA
    J Neurosci 21:5944-51. 2001
    ..Our results suggest that functional and pharmacological criteria used commonly to distinguish among different Ca currents greatly underestimate the biological importance of L-type channels in cells expressing Ca(v)1.3alpha(1)...
  8. ncbi Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels
    G S Pitt
    Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305, USA
    J Biol Chem 276:30794-802. 2001
    ..When the C-terminal lobe of CaM binds to the nearby CaM effector sequence (IQ motif), the braking effect is relieved, and CDI is accelerated...
  9. ncbi Unified mechanisms of Ca2+ regulation across the Ca2+ channel family
    Haoya Liang
    Ca2 Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Neuron 39:951-60. 2003
    ....
  10. ncbi Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels
    J Platzer
    Institut fur Biochemische Pharmakologie, Innsbruck, Austria
    Cell 102:89-97. 2000
    ..We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity...
  11. pmc A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation
    Ariana Hemara-Wahanui
    Biochemistry Department, University of Otago, P O Box 56, Dunedin, Aotearoa New Zealand
    Proc Natl Acad Sci U S A 102:7553-8. 2005
    ..Collectively, these findings suggest that a gain-of-function mechanism involving increased Ca(v)1.4 channel activity is likely to cause the unusual phenotype...
  12. ncbi An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness
    T M Strom
    Abteilung Medizinische Genetik der Ludwig Maximilians Universität, Munchen, Germany
    Nat Genet 19:260-3. 1998
    ..These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2...
  13. ncbi CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells
    Andreas Brandt
    Department of Otolaryngology, Goettingen University Medical School, 37075 Goettingen, Germany
    J Neurosci 23:10832-40. 2003
    ..We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission...
  14. ncbi Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness
    N T Bech-Hansen
    Department of Medical Genetics, University of Calgary, Alberta, Canada
    Nat Genet 19:264-7. 1998
    ..These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina...
  15. ncbi Ionic mechanisms of electrical remodeling in human atrial fibrillation
    R F Bosch
    Department of Cardiology, University of Tubingen, Germany
    Cardiovasc Res 44:121-31. 1999
    ..The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood...
  16. ncbi Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells
    P Safa
    Department of Pharmacology, The George Washington University, Washington, DC 20037, USA
    J Biol Chem 276:38727-37. 2001
    ..Furthermore, the QXXER motif, located on the C terminus of alpha(1D-S) subunit, is not sufficient to confer sensitivity to inhibitory G proteins...
  17. ncbi Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization
    Jason D Foell
    Department of Medicine, University of Wisconsin, Madison 53792, USA
    Physiol Genomics 17:183-200. 2004
    ..These results demonstrate a previously unappreciated heterogeneity of Ca(v)beta subunit isoforms in ventricular myocytes and suggest the presence of different subcellular populations of Ca2+ channels with distinct functional properties...
  18. ncbi Analysis of the complex between Ca2+ channel beta-subunit and the Rem GTPase
    Brian S Finlin
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky 40536 0509, USA
    J Biol Chem 281:23557-66. 2006
    ....
  19. ncbi Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel
    Jennifer L Fallon
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Structure 13:1881-6. 2005
    ..These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF...
  20. pmc Autoinhibitory control of the CaV1.2 channel by its proteolytically processed distal C-terminal domain
    Joanne T Hulme
    Department of Pharmacology, Mailstop 357280, University of Washington, Seattle, 98195 7280, USA
    J Physiol 576:87-102. 2006
    ..2 channel function...
  21. pmc Phosphorylation of serine 1928 in the distal C-terminal domain of cardiac CaV1.2 channels during beta1-adrenergic regulation
    Joanne T Hulme
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280, USA
    Proc Natl Acad Sci U S A 103:16574-9. 2006
    ..Our results correlate phosphorylation of S1928 with beta1-adrenergic functional up-regulation of cardiac calcium channels in the presence of BAPTA in intact ventricular myocytes...
  22. pmc Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity
    Matteo E Mangoni
    Unité Propre de Recherche 1142, Centre National de la Recherche Scientifique, Institut de Genetique Humaine, 141 rue de la Cardonille, Montpellier Cedex 5, France
    Proc Natl Acad Sci U S A 100:5543-8. 2003
    ..Taken together, our data demonstrate that Ca(v)1.3 channels play a major role in the generation of cardiac pacemaker activity by contributing to diastolic depolarization in SAN pacemaker cells...
  23. ncbi Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells
    Andrea Marcantoni
    Department of Neuroscience, Nanostructured Interfaces and Surfaces Centre of Excellence, Consorzio Nazionale Interuniversitario per le Scienze Fisiche della Materia, 10125 Torino, Italy
    J Neurosci 30:491-504. 2010
    ..2, as subthreshold pacemaker channels in MCCs and open new interesting features about their role in the control of firing and catecholamine secretion at rest and during sustained stimulations matching acute stress...
  24. ncbi Functional stoichiometry and local enrichment of calmodulin interacting with Ca2+ channels
    Masayuki X Mori
    Ca2 Signals Laboratory, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Science 304:432-5. 2004
    ..This estimate indicates marked enrichment of local CaM, as if a "school" of nearby CaMs were poised to enhance the transduction of local Ca2+ entry into diverse signaling pathways...
  25. pmc The skeletal L-type Ca(2+) current is a major contributor to excitation-coupled Ca(2+) entry
    Roger A Bannister
    Department of Physiology and Biophysics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
    J Gen Physiol 133:79-91. 2009
    ..Collectively, these results indicate that the skeletal muscle L-type channel is a major contributor to the Ca(2+) entry attributed to ECCE...
  26. ncbi The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution
    John E McRory
    Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 24:1707-18. 2004
    ..Immunohistochemical analyses show that, in contrast with previous reports, Ca(v)1.4 is widely distributed outside the retina, including in the immune system, thus suggesting a broader role in human physiology...
  27. ncbi Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C
    T J Kamp
    Department of Medicine, University of Wisconsin, Madison, WI 53792 3248, USA
    Circ Res 87:1095-102. 2000
    ..Crosstalk between PKA and PKC pathways occurs in the modulation of I:(Ca). Ultimately, precise regulation of I:(Ca) is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease...
  28. ncbi Atrial L-type Ca2+ currents and human atrial fibrillation
    D R Van Wagoner
    Department of Cardiology and Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Circ Res 85:428-36. 1999
    ..The reduction in functional I(Ca) density in myocytes from the atria of chronic AF patients may thus be an adaptive response to the arrhythmia-induced calcium overload...
  29. ncbi Congenital stationary night blindness type 2 mutations S229P, G369D, L1068P, and W1440X alter channel gating or functional expression of Ca(v)1.4 L-type Ca2+ channels
    Jean Charles Hoda
    Abteilung Pharmakologie und Toxikologie, Institut fur Pharmazie, Universitat Innsbruck, A 6020 Innsbruck, Austria
    J Neurosci 25:252-9. 2005
    ..The lower activation range of G369D can explain the reduced dynamic range of photoreceptor signaling. Moreover, we demonstrate that loss of channel function of one (L1068P) CSNB2 mutation can be rescued by a Ca2+ channel activator...
  30. ncbi alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages
    A Koschak
    Institut fur Biochemische Pharmakologie, Peter Mayr Strasse 1, A 6020 Innsbruck, Austria
    J Biol Chem 276:22100-6. 2001
    ..These properties should allow D-LTCCs to control physiological processes, such as diastolic depolarization in sinoatrial node cells, neurotransmitter release in IHCs and neuronal excitability...
  31. ncbi Structural and functional abnormalities of retinal ribbon synapses due to Cacna2d4 mutation
    Katharina A Wycisk
    Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
    Invest Ophthalmol Vis Sci 47:3523-30. 2006
    ..Rod photoreceptor responses were maintained with reduced amplitude, whereas cone activities were absent. This study was conducted to identify the genetic defect underlying this hitherto unknown autosomal recessive cone-rod dysfunction...
  32. ncbi Tuning of synapse number, structure and function in the cochlea
    Alexander C Meyer
    InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain, University of Gottingen, Gottingen, Germany
    Nat Neurosci 12:444-53. 2009
    ..However, we observed substantial variability for presynaptic Ca(2+) signals, even within individual IHCs, providing a candidate presynaptic mechanism for the divergent dynamics of spiral ganglion neuron spiking...
  33. ncbi L-type calcium channels: the low down
    Diane Lipscombe
    Department of Neuroscience, Brown University, 190 Thayer Street, Providence, RI 02912, USA
    J Neurophysiol 92:2633-41. 2004
    ..A more accurate view of neuronal L-type calcium channels encompasses a broad range of activation thresholds and recognizes their potential contribution to signaling cascades triggered by subthreshold depolarizations...
  34. pmc Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
    Hiroyuki Nakayama
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
    J Clin Invest 117:2431-44. 2007
    ....
  35. ncbi Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models
    Michelle Day
    Department of Physiology, 303 East Chicago Avenue, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Nat Neurosci 9:251-9. 2006
    ..3 L-type Ca(2+) channels. The disconnection of striatopallidal neurons from motor command structures is likely to be a key step in the emergence of pathological activity that is responsible for symptoms in Parkinson disease...
  36. pmc Constitutively active L-type Ca2+ channels
    Manuel F Navedo
    Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 102:11112-7. 2005
    ..We propose that Ca(2+) influx via persistent LTCCs may be an important mechanism regulating steady-state local and global Ca(2+) signals...
  37. ncbi Regulation of L-type Ca2+ channel activity and insulin secretion by the Rem2 GTPase
    Brian S Finlin
    Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, Kentucky 40536, USA
    J Biol Chem 280:41864-71. 2005
    ....
  38. ncbi A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants
    K M Boycott
    Department of Medical Genetics, University of Calgary, AB, Canada
    Hum Genet 108:91-7. 2001
    ..In characterizing transcripts of CACNA1F we have identified several splice variants and defined a prototypical sequence based on the location of mutations in splice variants and comparison with the mouse orthologue, Cacnalf...
  39. ncbi 17Beta-estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: a potential initiation mechanism for estrogen-induced neurop
    T W Wu
    Neuroscience Program, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089 9121, USA
    Neuroscience 135:59-72. 2005
    ..Implications of these data for understanding estrogen action in brain and use of estrogen therapy for prevention of neurodegenerative disease are discussed...
  40. pmc A single CaVbeta can reconstitute both trafficking and macroscopic conductance of voltage-dependent calcium channels
    Stanislava Dalton
    Calcium Signals Laboratory, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Physiol 567:757-69. 2005
    ....
  41. ncbi Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage-dependent Ca2+ channels in retinal pigment epithelial cells
    Rita Rosenthal
    Augenklinik, Charite Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
    FASEB J 20:178-80. 2006
    ....
  42. pmc Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
    Igor Splawski
    Howard Hughes Medical Institute, Department of Cardiology, and Genomics Program and Division of Genetics, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8089-96; discussion 8086-8. 2005
    ..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS...
  43. ncbi Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F
    K M Boycott
    Department of Medical Genetics, Faculty of Medicine, University of Calgary, Alta
    Can J Ophthalmol 35:204-13. 2000
    ..We assessed the clinical variability in the expression of the incomplete CSNB phenotype in a subgroup of patients of Mennonite ancestry with the same founder mutation...
  44. ncbi Neurophysiology: stressful pacemaking
    Bruce P Bean
    Nature 447:1059-60. 2007
  45. ncbi Meiosis reinitiation in Ruditapes philippinarum (Mollusca): involvement of L-calcium channels in the release of metaphase I block
    M Moreau
    Universite Paul Sabatier, Toulouse, France
    Zygote 4:151-7. 1996
    ..Taken together these data suggest that the absence of L-type calcium channels in the membrane of prophase-arrested oocytes of Ruditapes may account for their inability to be fertilised...
  46. ncbi The voltage-dependent calcium channel beta subunit contains two stable interacting domains
    Yarden Opatowsky
    Department of Biochemistry, Faculty of Life Sciences, Tel Aviv University, Sherman Bldg, Rm 621, Ramat Aviv 69978, Israel
    J Biol Chem 278:52323-32. 2003
    ..Domain II is responsible for this binding, but domain I enhances it...
  47. ncbi Syntaxin 1A modulates the voltage-gated L-type calcium channel (Ca(v)1.2) in a cooperative manner
    Hadar Arien
    Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    J Biol Chem 278:29231-9. 2003
    ..As shown herein, the supralinear relationship between Sx1A and the voltage-gated Ca2+ channel within the cluster could convey the cooperativity that distinguishes the process of neurotransmitter release...
  48. ncbi Computer model of action potential of mouse ventricular myocytes
    Vladimir E Bondarenko
    Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214 3078, USA
    Am J Physiol Heart Circ Physiol 287:H1378-403. 2004
    ..The attribution of putative molecular bases for several of the component currents enables our mouse model to be used to simulate the behavior of genetically modified transgenic mice...
  49. pmc Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells
    Guiying Cui
    Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Physiol 585:791-803. 2007
    ..3 Ca(2+) currents required for auditory transmission...
  50. pmc Protein phosphatase 1 and an opposing protein kinase regulate steady-state L-type Ca2+ current in mouse cardiac myocytes
    William H duBell
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Physiol 556:79-93. 2004
    ....
  51. pmc Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store
    Olivier Thibault
    Department of Molecular and Biomedical Pharmacology, University of Kentucky, University of Kentucky Medical Center, Lexington, KY 40536, USA
    Aging Cell 6:307-17. 2007
    ..In turn, the increased transients result in dysregulation of multiple Ca2+-dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD...
  52. ncbi L-type calcium channel alpha-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current
    Shawn M Crump
    Dept of Physiology, MS 508, Univ of Kentucky College of Medicine, 800 Rose St Lexington, KY 40536 0298, USA
    Am J Physiol Heart Circ Physiol 291:H1959-71. 2006
    ..We conclude that Rem is capable of regulating L-type current, that release of Rem block is modulated by cellular kinase pathways, and that the Ca(V)1.2 COOH terminus contributes to Rem-dependent channel inhibition...
  53. pmc Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels
    Martina J Sinnegger-Brauns
    Abteilung Pharmakologie und Toxikologie, Institut fur Pharmazie, Universitat Innsbruck, Austria
    J Clin Invest 113:1430-9. 2004
    ..This animal model provides a useful tool to elucidate whether Ca(v)1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects...
  54. ncbi Transcript scanning reveals novel and extensive splice variations in human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit
    Zhen Zhi Tang
    Department of Physiology, National University of Singapore, Singapore 117597
    J Biol Chem 279:44335-43. 2004
    ..This systematic portrait of splice variation furnishes a reference library for comprehending combinatorial arrangements of Cav1.2 splice exons, especially as they impact development, physiology, and disease...
  55. ncbi Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W
    J B Peloquin
    Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, HMRB 172b, 3330 Hospital Drive Northwest, Calgary, Alberta, Canada T2N 4N1
    Neuroscience 150:335-45. 2007
    ..These findings suggest that the pathology of CSNB-2 in patients with these missense mutations in the Ca(v)1.4 calcium channel is the result in either a gain of function (F742C) or a loss of function (G1007R, R1049W)...
  56. ncbi Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79
    Christophe Altier
    Physiopathologie des Canaux Ioniques, Institut de Génétique Humaine CNRS UPR1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    J Biol Chem 277:33598-603. 2002
    ....
  57. pmc Intramembrane charge movement and L-type calcium current in skeletal muscle fibers isolated from control and mdx mice
    C Collet
    Laboratoire de Physiologie des Elements Excitables, Universite Claude Bernard, F69622 Villeurbanne, France
    Biophys J 84:251-65. 2003
    ..They may be speculated to result, at least in part, from remodeling of the submembranous cytoskeleton network due to the absence of dystrophin...
  58. ncbi A novel CACNA1F gene mutation causes Aland Island eye disease
    Reetta Jalkanen
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
    Invest Ophthalmol Vis Sci 48:2498-502. 2007
    ..The purpose of this study was to identify the mutated gene underlying the disease phenotype in the original AIED-affected family...
  59. ncbi Expression of voltage-dependent calcium channel subunits in the rat retina
    Hong Ping Xu
    Institute of Neurobiology, Fudan University, Shanghai 200433, PR China
    Neurosci Lett 329:297-300. 2002
    ..Staining for alpha(1D) was also observed on Müller cells. The differential expression pattern of the alpha(1) subunits suggests that these Ca(2+) channel subtypes may be associated with different retinal functions...
  60. ncbi Molecular characterization of a neuronal low-voltage-activated T-type calcium channel
    E Perez-Reyes
    Department of Physiology, and Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA
    Nature 391:896-900. 1998
    ..Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel...
  61. ncbi Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases
    K D Keef
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Am J Physiol Cell Physiol 281:C1743-56. 2001
    ....
  62. ncbi Tottering mouse motor dysfunction is abolished on the Purkinje cell degeneration (pcd) mutant background
    D B Campbell
    Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Exp Neurol 160:268-78. 1999
    ..These data suggest that the cerebellar cortex, where the mutant gene is abundantly expressed, contributes to the expression of tottering mouse dystonic episodes...
  63. ncbi Calcium handling abnormalities in atrial fibrillation as a target for innovative therapeutics
    Dobromir Dobrev
    Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany
    J Cardiovasc Pharmacol 52:293-9. 2008
    ..This review focuses on the molecular basis of altered Ca handling in AF, with the goal of providing new insights into molecular effective antiarrhythmic therapy...
  64. ncbi Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach
    Laura Sartiani
    Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata, University of Firenze, Firenze, Italy
    Stem Cells 25:1136-44. 2007
    ..In summary, human embryonic stem cell-derived cardiomyocytes mature over time during in vitro differentiation, approaching an adult phenotype. Disclosure of potential conflicts of interest is found at the end of this article...
  65. pmc Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder
    Annette Hohaus
    Institute for Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Wien
    J Biol Chem 280:38471-7. 2005
    ..2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating...
  66. pmc Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15
    Joanne T Hulme
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    Proc Natl Acad Sci U S A 100:13093-8. 2003
    ....
  67. ncbi Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+ transients and contraction in cardiomyocytes derived from embryonic stem cells
    Ji Dong Fu
    Laboratory of Molecular Cardiology of Institute of Health Sciences, Shanghai Institutes for Biological Sciences SIBS, Chinese Academy of Sciences CAS and Shanghai Jiao Tong University School of Medicine, Shanghai, China
    FASEB J 20:181-3. 2006
    ..We conclude that functional SR and control of RyR2-mediated SR Ca2+ release directly contribute to the spontaneous and beta-adrenergic receptor-stimulated contraction of ESCMs, even at very immature stages of development...
  68. ncbi IP(3) receptor function and localization in myotubes: an unexplored Ca(2+) signaling pathway in skeletal muscle
    J A Powell
    Department of Biological Sciences, Smith College, Northampton, MA 01063, USA
    J Cell Sci 114:3673-83. 2001
    ..These results suggest a signaling system mediated by Ca(2+) and inositol trisphosphate that could regulate gene expression in muscle cells...
  69. pmc Conformational activation of Ca2+ entry by depolarization of skeletal myotubes
    Gennady Cherednichenko
    Department of Molecular Biosciences and Center for Children s Environmental Health and Disease Prevention, University of California, Davis, CA 95616, USA
    Proc Natl Acad Sci U S A 101:15793-8. 2004
    ..ECCE may provide a fundamental means to rapidly maintain Ca(2+) stores and control important aspects of Ca(2+) signaling in both muscle and nonmuscle cells...
  70. ncbi Growth and function of the embryonic heart depend upon the cardiac-specific L-type calcium channel alpha1 subunit
    W Rottbauer
    Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Dev Cell 1:265-75. 2001
    ..Thus, calcium signaling via C-LTCC can regulate heart growth independently of contraction, and plays distinctive roles in fashioning both form and function of the two developing chambers...
  71. ncbi Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina
    Krisztina Wutz
    Abteilung Medizinische Genetik der LMU, Munchen, Germany
    Eur J Hum Genet 10:449-56. 2002
    ..Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission...
  72. ncbi BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling
    Henrike Berkefeld
    Institute of Physiology, University of Freiburg, Hermann Herder Strasse 7, 79104 Freiburg, Germany
    Science 314:615-20. 2006
    ..Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system...
  73. ncbi Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice
    Laetitia Pereira
    Institut National de la Santé et de la Recherche Médicale U 637, University of Montpellier 1, France
    Diabetes 55:608-15. 2006
    ..As less Ca2+ enters the cell through I(Ca), less Ca2+ is released through RyRs...
  74. ncbi Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression
    Jason P Weick
    Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Neurosci 23:3446-56. 2003
    ..Collectively, these data suggest that localized calcium responses, regulated by interactions with PDZ domain proteins, are necessary for L-type calcium channels to effectively activate CREB and CRE-mediated gene expression...
  75. pmc Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function
    Francoise Haeseleer
    Department of Ophthalmology, University of Washington, Box 356485, Seattle, Washington 98195, USA
    Nat Neurosci 7:1079-87. 2004
    ..These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals...
  76. ncbi Genomic deletion of estrogen receptors ERalpha and ERbeta does not alter estrogen-mediated inhibition of Ca2+ influx and contraction in murine cardiomyocytes
    Nina D Ullrich
    Imperial College London, Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom
    Am J Physiol Heart Circ Physiol 294:H2421-7. 2008
    ..Decreases in cell shortening occurred in parallel with these findings. Our results suggest that inhibition of ICaL and the decrease in contraction by estrogens do not depend on ERalpha or ERbeta...
  77. ncbi Molecular identity, synaptic localization, and physiology of calcium channels in retinal bipolar cells
    Amy Berntson
    John Curtin School of Medical Research, Australian National University, Canberra, Australia
    J Neurosci Res 71:146-51. 2003
    ..The L-type current may be mediated by the alpha(1F) subunit, and influx of calcium through the alpha(1F) channel may control neurotransmitter release from the bipolar cell terminal...
  78. ncbi Regulation of insulin secretion in islets of Langerhans by Ca(2+)channels
    David Mears
    Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA
    J Membr Biol 200:57-66. 2004
    ..The emerging picture is that Ca(2+) channels regulate insulin secretion at multiple sites in the stimulus-secretion coupling pathway, with the specific role of each channel determined by its biophysical and structural properties...
  79. ncbi Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory
    Sven Moosmang
    Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, 80802 Munich, Germany
    J Neurosci 25:9883-92. 2005
    ..2 channel-mediated Ca2+ influx to either process...
  80. pmc Coupled and independent contributions of residues in IS6 and IIS6 to activation gating of CaV1.2
    Michaela Kudrnac
    Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Wien, Austria
    J Biol Chem 284:12276-84. 2009
    ..8 +/- 1.4 mV). Mutant cycle analysis revealed energetic coupling between residues Ser-435 and Ile-781, whereas other paired mutations in segments IS6 and IIS6 had independent effects on activation gating...
  81. pmc A retrograde signal from RyR1 alters DHP receptor inactivation and limits window Ca2+ release in muscle fibers of Y522S RyR1 knock-in mice
    Zoita Andronache
    Institute of Applied Physiology, Ulm University, D 89069 Ulm, Germany
    Proc Natl Acad Sci U S A 106:4531-6. 2009
    ....
  82. pmc Inhibitory control over Ca(2+) sparks via mechanosensitive channels is disrupted in dystrophin deficient muscle but restored by mini-dystrophin expression
    Martin D H Teichmann
    Medical Biophysics, Department of Systems Physiology, Institute of Physiology and Pathophysiology, Ruprecht Karls University, Heidelberg, Germany
    PLoS ONE 3:e3644. 2008
    ..They may be related to mechanosensitive pathways but the mechanisms are elusive. Also, it is not known whether truncated dystrophins can correct the dystrophic disinhibition...
  83. ncbi The three-dimensional structure of the cardiac L-type voltage-gated calcium channel: comparison with the skeletal muscle form reveals a common architectural motif
    Ming Chuan Wang
    Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK
    J Biol Chem 279:7159-68. 2004
    ..A difference between the cardiac and skeletal muscle ion channels is apparent in the putative transmembrane region, which would be consistent with the absence of the gamma subunit in the cardiac VGCC assembly...
  84. pmc Probing the architecture of an L-type calcium channel with a charged phenylalkylamine: evidence for a widely open pore and drug trapping
    Stanislav Beyl
    Institute for Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Vienna, Austria
    J Biol Chem 282:3864-70. 2007
    ..The functional data indicating a location of a trapped (-)D888 molecule close to the central pore region are supported by a homology model illustrating that the closed Ca(v)1.2 is able to accommodate a large cation such as (-)D888...
  85. ncbi Switching of Ca2+-dependent inactivation of Ca(v)1.3 channels by calcium binding proteins of auditory hair cells
    Philemon S Yang
    Ca2 Signals Laboratory, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 26:10677-89. 2006
    ..In particular, the rare subtype CaBP4 is specific to IHCs, and CaBP4 proves capable of eliminating even the potent baseline CDI of Ca(V)1.3. CaBP4 thereby represents a plausible candidate for moderating CDI within IHCs...
  86. pmc Control of ion conduction in L-type Ca2+ channels by the concerted action of S5-6 regions
    Susan M Cibulsky
    Department of Pharmacology and Program in Neuroscience, University of Colorado Health Sciences Center, Denver 80262, USA
    Biophys J 84:1709-19. 2003
    ..Moreover, the pattern of unitary conductance values obtained for chimeras in which a single P-loop or single S5-6 region was replaced suggest a concerted action of pore-lining regions in the control of ion conduction...
  87. ncbi Voltage-dependent calcium channels
    L Lacinova
    Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava 37, Slovakia
    Gen Physiol Biophys 24:1-78. 2005
    ..Transfer of 30 % of charge correlates with activation of 70 % of measurable macroscopic current. Prolonged depolarization does not immobilize charge movement of the Ca(v)3.1 channel...
  88. ncbi Temperature dependence of Cav1.4 calcium channel gating
    J B Peloquin
    Department of Physiology and Biophysics, Hotchkiss Brain Institute, HMRB 172b, 3330 Hospital Drive Northwest, University of Calgary, Calgary, Alberta, Canada T2N4N1
    Neuroscience 151:1066-83. 2008
    ..4 channels observed at near physiological temperatures the window current is preserved and could allow for tonic glutamate release from photoreceptors in the retina during dark adapted conditions...
  89. ncbi G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain
    Patricia A Olson
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 25:1050-62. 2005
    ..Together, these results suggest that Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+ channels and the integration of glutamatergic synaptic events...
  90. ncbi Subunit expression of the cardiac L-type calcium channel is differentially regulated in diastolic heart failure of the cardiac allograft
    R Hullin
    Department of Internal Medicine, University Hospital Grobetahadern, Munich, Germany
    Circulation 100:155-63. 1999
    ..Multimeric L-type calcium channels (alpha1-, alpha2/delta-, and beta-subunits) are essential for excitation/contraction coupling in the heart. Their gene expression was studied in allografts that developed diastolic heart failure...
  91. ncbi Disulfide bonds, N-glycosylation and transmembrane topology of skeletal muscle triadin
    H Fan
    Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33136, USA
    Biochemistry 34:14902-8. 1995
    ..The glycosidase endo F/N-glycosidase F changed the mobility of intact triadin in TC/triads and its proteolytic fragments detected by mAb GE4.90.(ABSTRACT TRUNCATED AT 250 WORDS)..
  92. pmc Location of ryanodine and dihydropyridine receptors in frog myocardium
    Pierre Tijskens
    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6058, USA
    Biophys J 84:1079-92. 2003
    ..Interestingly, the free SR membrane in both heart chambers shows a low but equal density of intramembrane particles representing the Ca(2+) ATPase...
  93. ncbi A small-molecule screen in C. elegans yields a new calcium channel antagonist
    Trevor C Y Kwok
    Department of Medical Genetics and Microbiology, and The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
    Nature 441:91-5. 2006
    ..Our study demonstrates that C. elegans enables rapid identification of new small-molecule tools and their targets...
  94. ncbi Functional properties of ryanodine receptors in hippocampal neurons change during early differentiation in culture
    Manana Sukhareva
    Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Neurophysiol 88:1077-87. 2002
    ..The mode of activation of L-type voltage-gated Ca(2+) channels with either membrane depolarization or specific pharmacological agents affects the coupled activity of RyRs differently as neurons differentiate processes and networks...
  95. ncbi The transmembrane domain of syntaxin 1A negatively regulates voltage-sensitive Ca(2+) channels
    M Trus
    Department of Biological Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel
    Neuroscience 104:599-607. 2001
    ..Cleavage with botulinum toxin disrupts the coupling of the N- and Lc-type channels with syntaxin 1A and abolishes exocytosis, supporting the hypothesis that these channels actively participate in Ca(2+) regulated secretion...
  96. ncbi Temperature-sensitive intracellular Mg2+ block of L-type Ca2+ channels in cardiac myocytes
    Kaoru Yamaoka
    Department of Physiology, School of Medicine, Hiroshima University, Minami Ku, Hiroshima 734 8551, Japan
    Am J Physiol Heart Circ Physiol 282:H1092-101. 2002
    ..This effect of phosphorylation together with the inhibitory action of GTP(i) on Mg2+-dependent blocking of I(Ca) are common properties of mammalian and amphibian cardiomyocytes...
  97. pmc Cytochalasin D reduces Ca2+ currents via cofilin-activated depolymerization of F-actin in guinea-pig cardiomyocytes
    U Rueckschloss
    Department of Physiology, Faculty of Medicine, Martin Luther University, 06097 Halle, Germany
    J Physiol 537:363-70. 2001
    ..6. The data support the concept that cytD mediates dephosphorylation and activation of ADF/cofilin, leading to depolymerization of F-actin with a subsequent reduction of I(Ca)...
  98. ncbi A novel long N-terminal isoform of human L-type Ca2+ channel is up-regulated by protein kinase C
    Yakov Blumenstein
    Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
    J Biol Chem 277:3419-23. 2002
    ..The long-NT isoform may be the Ca(2+) channel enhanced by PKC-activating transmitters in human tissues...
  99. ncbi The voltage-gated Ca2+ channel is the Ca2+ sensor of fast neurotransmitter release
    D Atlas
    Department of Biological Chemistry, Hebrew University of Jerusalem, Israel
    Cell Mol Neurobiol 21:717-31. 2001
    ..The results imply a rapid Ca2+-dependent CAV (RRP) release, initiated by the binding of Ca2+ to the channel, upstream to intracellular Ca2+ sensor thus establishing the Ca2+ channel as the Ca2+ sensor of neurotransmitter release...
  100. ncbi Altered communication between L-type calcium channels and ryanodine receptors in heart failure
    Jean Pierre Benitah
    INSERM U 390, Montpellier, France
    Front Biosci 7:e263-75. 2002
    ..This theory is supported by new data showing that the T-tubule density is reduced in failing cells...
  101. pmc The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels
    Curtis F Barrett
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305 5345, USA
    Proc Natl Acad Sci U S A 105:2157-62. 2008
    ..Thus, the TS mutation offers a unique perspective on mechanisms of inactivation as well as a promising starting point for exploring the underlying pathophysiology of autism...

Research Grants63

  1. Molecular physiology of voltage-gated Ca2+ channels
    Jian Yang; Fiscal Year: 2013
    ..By studying a novel form of activity-dependent fragmentation of VGCCs on the cell membrane, this work may lead to a better understanding of VGCC function and regulation in physiological and pathological conditions. ..
  2. Functional Studies of Variants of the Bipolar Risk Gene CACNA1C in Human Neurons
    JEN PAN; Fiscal Year: 2013
    ....
  3. Mineralocorticoid Receptor-Mediated Vascular Insulin Resistance
    SHAWN BRADY BENDER; Fiscal Year: 2013
    ..IR will be induced in wild-type and VSMC MR KO mice with a high-fat, high-sucrose diet and will be assessed by glucose tolerance testing. ..
  4. Chronic stress-induced gene expression in colonic circular smooth muscle cells.
    Sushil K Sarna; Fiscal Year: 2012
    ..The findings of this proposal are expected to identify the potential molecular therapeutic approaches that may prevent or minimize the ill effects of chronic stress on colonic motility function. ..
  5. Calcium Signaling, Metabolism, and EC Coupling in Heart
    Joshua I Goldhaber; Fiscal Year: 2013
    ..This will lead to new therapeutic strategies for preserving heart muscle function, thereby reducing the incidence of heart failure. ..
  6. Caveolae and mitochondria: A structural interface functionally linking calcium an
    GREGORY CHARLES AMBERG; Fiscal Year: 2013
    ..The outcome of these experiments will provide mechanistic insights into events underlying arterial dysfunction in obesity and may lead to the development of new rational therapies for managing and preventing cardiovascular disease. ..
  7. Roles of voltage sensor, S100A1 and calmodulin in skeletal muscle Ca2+ signaling
    Martin F Schneider; Fiscal Year: 2013
    ..Thus, this project has high impact for multiple disciplines, and for problems of both locomotion and breathing common to a variety of advanced diseased states and aging. ..
  8. Gonadal Hormones and Depression:The Role of Mood Disorder Risk Gene CACNA1C
    Todd D Gould; Fiscal Year: 2012
    ....
  9. VIP-induced gene expression in colonic smooth muscle cells
    Sushil K Sarna; Fiscal Year: 2010
    ..abstract_text> ..
  10. AKAP Regulation of Neuronal L-type Calcium Channel Signaling to the Nucleus
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ....
  11. Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels
    Kristin Webster; Fiscal Year: 2013
    ..I hypothesize that the e1b isoform will more efficiently induce CREB phosphorylation. These experiments will advance our understanding of how neuronal specific isoforms of CaV1.2 contribute to essential neuronal functions. ..
  12. GABA-B Receptor Modulation of Calcium Currents
    Michelle Mynlieff; Fiscal Year: 2010
    ..but these compounds also cause side effects such as drowsiness, mental slowing, and double vision. By increasing our understanding of the specific effects of GABA, it will be possible to design better drugs for these types of disorders. ..
  13. CLASSICAL AND ALTERNATIVE PATHWAYS OF FIBRINOLYSIS
    EDWARD FRANKLIN PLOW; Fiscal Year: 2013
    ..Taken together, these studies will define how plasminogen and its receptors function in biologically important responses. ..
  14. Chemokine receptor-4 regulation of Beta adrenergic-mediated calcium channel
    Sima T Tarzami; Fiscal Year: 2012
    ....
  15. Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
    John Y Kuwada; Fiscal Year: 2013
    ..This knowledge should help us better understand the biology of myopathies and could potentially lead to therapeutic agents for congenital myopathies. ..
  16. Cerebral artery Ca2+ signaling & subarachnoid hemorrhage
    George Wellman; Fiscal Year: 2009
    ..This study should significantly enhance current knowledge with respect to Ca2+signaling and constriction of cerebral arteries in health and disease and provide insight into possible new therapies for the treatment of cerebral vasospasm. ..
  17. Manganese-Enhanced MRI Studies of Vision Loss with Aging
    DAVID PHILIP BISSIG; Fiscal Year: 2013
    ..abstract_text> ..
  18. Regulation of Cardiac Gene Expression by the L-type Calcium Channel, CaV1.2.
    ROBERT NATHAN CORRELL; Fiscal Year: 2011
    ..This work will help reveal the role of the cardiac L-type Ca2+ channel in regulation of gene expression related to disease and may suggest new translational strategies to combat heart failure. ..
  19. Regulation of L-type calcium channels by CaBP4
    FRANCOISE J HAESELEER; Fiscal Year: 2013
    ..These studies will fill a major void in our understanding of factors controlling photoreceptor Cav1 channels and how dysregulation of these channels may lead to CSNB2 and potentially other visual disorders. ..
  20. Pathophysiology of dystonia: animal models
    Ellen J Hess; Fiscal Year: 2010
    ..Public health relevance: Dystonia is the third most common movement disorder, but current therapies are largely unsatisfactory. The goal is to understand the pathophysiology of dystonia to direct novel treatments. ..
  21. Secretagogue induced mechanisms regulating islet electrical activity
    DAVID AARON JACOBSON; Fiscal Year: 2012
    ..Understanding how secretagogues regulate islet electrical activity distinctly from KATP may help to develop new therapies that target specific elements of the excitation-secretion pathway. ..
  22. Improving Cardiac Regeneration Using Stem Cells with Enhanced Calcium Influx
    Sharven Taghavi; Fiscal Year: 2012
    ..Once proof of concept studies has been done in mice and if efficacy is shown in the 22a infected stem cells, they will also be tested in a porcine model. ..
  23. Structure of Channels in Excitation-Contracting Coupling
    TERENCE C WAGENKNECHT; Fiscal Year: 2013
    ..This proposal will use advanced electron microscopy technology to characterize the structural organization and interactions among these proteins. The findings will be important for understanding normal and diseased muscle function. ..
  24. Single nucleotide polymorphisms of neuronal CACNA1C L-type calcium channels assoc
    Diane Lipscombe; Fiscal Year: 2011
    ..We will use a combination of RNA, gene, and electrophysiological analyses to reveal the functional role of intron 4 in controlling L-type calcium channel activity in neurons. ..
  25. L-type Ca2+ Channel Modulation of Beta Cell Function
    GREGORY HOWARD HOCKERMAN; Fiscal Year: 2012
    ..This proposal is consistent with the PI's long term goal of understanding L-type calcium channel modulation and cellular function. ..
  26. D1 Dopamine Receptor Signaling and Cocaine Reinstatement
    ROBERT CHRISTOPHER PIERCE; Fiscal Year: 2012
    ....
  27. Role of Calcium Channels in Aging Skeletal Muscle
    Osvaldo Delbono; Fiscal Year: 2012
    ..Claudia Hereqz at the National University of La Plata, Argentina to elucidate the cellular and molecular mechanisms responsible for the decline in skeletal muscle performance with aging. ..
  28. Role of L-Type Calcium Channels in Hippocampal Neuronal Network Activity
    SCOTT OWEN; Fiscal Year: 2010
    ..We propose here a series of experiments to develop a deeper understanding of how one model of autism spectrum disorder might function at multiple levels from genes to molecules to neural circuits as they function in the brain. ..
  29. L-type Calcium Channels, Neuronal Excitability &Cognition in Aged Mice
    Geoffrey G Murphy; Fiscal Year: 2012
    ....
  30. Fibroblast Growth Factor Homologous Factors: Modulation of L-type Calcium Channel
    JESSICA AMENTA HENNESSEY; Fiscal Year: 2013
    ..This will demonstrate that FGF13 is a prominent player in the cardiac action potential through its modulation of the LTCC and define FGF13 dysfunction as a mediator of acquired and inherited arrhythmias. ..
  31. Coupled Gating of L-type Calcium Channels in Heart
    Luis F Santana; Fiscal Year: 2013
    ..This work will generate fundamental information on the mechanisms by which AKAP150 and Cav1.2 channels control of excitability, gene expression, and EC coupling in the heart under physiological and pathological conditions. ..
  32. Dopamine D2 Receptors in Prefrontal Function: An Optogenetic and Modeling Study
    IAN THOMAS ELLWOOD; Fiscal Year: 2013
    ..In addition, this model may be used to gain insight into perturbations of normal D2R function that have been hypothesized to underlie psychiatric diseases such as schizophrenia. ..
  33. Patterning and Formation of the Neuromuscular Junction
    Weichun Lin; Fiscal Year: 2013
    ..By identifying these regulatory signals, we may be able to provide additional targets for the development of therapeutic strategies to cure, control, or prevent neurodevelopmental disorders and neurodegenerative diseases. ..
  34. Analysis of the shocked zebrafish motility mutant
    Julia Dallman; Fiscal Year: 2009
    ..abstract_text> ..
  35. L-type Calcium Channel Regulation of Neuronal Differentiation
    Georgia Panagiotakos; Fiscal Year: 2012
    ..These studies will expand our understanding of how activity regulates brain development and will provide new insights into the underlying pathophysiology of autism and mental retardation. ..
  36. Calcium sparklets-induced vascular dysfunction during diabetes
    Manuel F Navedo; Fiscal Year: 2013
    ....
  37. Improving Buprenorphine Detoxification Outcomes with Isradipine
    Alison Oliveto; Fiscal Year: 2013
    ..This would shift clinical practice establishing an effective adjunct regimen for BUP detoxification as well as having the potential to enhance transition to naltrexone therapy. ..
  38. Modulators of CaV1.3 Ca2+ regulation
    David T Yue; Fiscal Year: 2013
    ..3) To test candidate compounds for modulation of CaV1.3 Ca2+ regulation, using patch-clamp electrophysiology. Overall, this project promises lead candidates for selective modulators of CaV1.3 versus other CaV1 L-type calcium channels. ..
  39. Pharmacogenetics and Cardiovascular Events
    Bruce Psaty; Fiscal Year: 2006
    ..The primary defense is replication: we would therefore welcome collaboration from others in the Pharmacogenetics Network in validation efforts. ..
  40. REGULATION OF NEURONAL CALCIUM CHANNELS
    JEFFRY LANSMAN; Fiscal Year: 2000
    ..The fourth Aim involves characterizations of the Ca2+i pools mobilized by mGluR1 and muscarinic receptors in granule cells and determine the contribution of store-coupled Ca2+ influx to electrical excitability. ..
  41. Cardiac Channels: Targets of Drugs that Affect Kinetics
    Dorothy A Hanck; Fiscal Year: 2010
    ..Our strategy combines mutagenesis, whole cell, single channel, and gating current electrophysiology, and molecular modeling. ..
  42. Lipid modulation of beta-cell calcium channels
    Lina Moitoso de Vargas; Fiscal Year: 2006
    ..We will separate the effects of FFA on different L-type VDCC and determine the effects of FFA on currents through mutant channels generated in Aim 2. ..
  43. PHYSIOLOGY AND IMMUNOHISTOCHEMISTRY OF DENTAL PULP
    Robert Davidson; Fiscal Year: 1999
    ..g., growth factors, dexamethasone, or DMSO, and patch-clamp recordings made in parallel with immunohistochemical studies using a monoclonal antibody to the sodium channel itself. ..
  44. BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION
    William Crowley; Fiscal Year: 2003
    ..abstract_text> ..
  45. IONIC CONTROL OF CARDIAC MUSCLE CONTRACTION: EC COUPLING
    Donald Bers; Fiscal Year: 2004
    ..This work will greatly increase fundamental understanding of key cardiac Ca transport systems in the intact cellular environment under physiological conditions. ..
  46. Fetal Coronary Vascular Responses to Long-term Hypoxia
    RAYMOND GILBERT; Fiscal Year: 2005
    ..Upon completion of the studies, we will have a better understanding of the alteration in fetal coronary artery contractility brought about by exposure to long-term hypoxemia. ..
  47. Role of MG29 in E-C Coupling of Striated Muscles
    Jianjie Ma; Fiscal Year: 2006
    ..In addition, our studies with the mutant mice will provide new insights into the cellular mechanism of muscle exercise physiology and cardiovascular diseases. ..
  48. DEVELOPING HEART--BIOPHYSICAL ASPECTS
    Page Anderson; Fiscal Year: 1999
    ....
  49. Neurobiology of Self-Injurious Behavior
    HYDER JINNAH; Fiscal Year: 2005
    ..These studies have direct relevance for understanding the neuroanatomical and neurochemical basis for self-injurious behavior and direct implications for a potential novel treatment strategy. ..
  50. Cannabinoid Receptors and Cerebrovascular Function
    Cecilia Hillard; Fiscal Year: 2006
    ..Increased understanding of the mediators that are released by activated microglia and their targets may provide new therapeutic approaches to CNS diseases with an inflammatory component. ..
  51. MUSCARINIC AND ADENOSINE RECEPTOR SIGNAL TRANSDUCTION
    Richard Mortensen; Fiscal Year: 2001
    ..These experiments should provide important information on the specificity of signal transduction by G proteins in heart. ..
  52. REGULATION OF THE CARDIAC CALCIUM CHANNEL
    James Marsh; Fiscal Year: 1993
    ..Gaining further understanding of mechanisms that regulate calcium channel expression is of fundamental biological importance and will have therapeutic implications...
  53. L-type Channel Calcium Entry Triggered Diastolic Calcium Sparks
    WILLIAM CECIL LESTER; Fiscal Year: 2010
    ..e. heart failure model). If time allows or if needed, simultaneous whole patch electrophysiology and calcium imaging can be used to dissect the two populations of diastolic sparks in the adult and their voltage dependence. ..
  54. ALCOHOL MODULATION OF CARDIAC CALCIUM CHANNELS
    Gary Aistrup; Fiscal Year: 2003
    ..This novel action may have major implications, given the widespread clinical use of dihydropyridines and other calcium channel antagonists. Drug interactions of this type will be an important focus of the project. ..
  55. Rapid Effects of Estradiol in the Brain
    Jill Becker; Fiscal Year: 2007
    ..It may also be important for our understanding and treatment of a number of neurological disorders including stroke, Alzheimer's disease and Parkinson's disease where estradiol may be neuroprotective. ..
  56. Myocardial Properties of Timothy Syndrome
    RANDALL RASMUSSON; Fiscal Year: 2009
    ..Patients with Timothy Syndrome die at an average age of 2.5 years. In order to better understand and treat this disorder we will study a mouse in which the same genetic defect has been artificially introduced. ..
  57. Reorganization of calcium signaling in heart failure
    Sandor Gyorke; Fiscal Year: 2007
    ..abstract_text> ..
  58. Role of Calcium in Cocaine-Induced Sensitization
    STEPHANIE LICATA; Fiscal Year: 2002
    ..Second, rats will receive either acute or repeated cocaine and relative abundance of either calmodulin or CaMKII will be measured in the VTA and substantia nigra using immunolabeling techniques. ..
  59. GORDON RES CONF: MUSCLE EXCITATION-CONTRACTION COUPLING
    David MacLennan; Fiscal Year: 2000
    ..The format encourages the exchange of ideas and unpublished data. The organizing committee, with representatives of varying ages from five continents, will strive to achieve appropriate representation of women. minorities and disabled. ..
  60. RELEASE CHANNEL ISOFORMS AND LOCAL CALCIUM SIGNALING
    Natalia Shirokova; Fiscal Year: 2003
    ..Proposed studies will greatly advanced our knowledge of their functioning, which in turn could improve our understanding of their role in decease. ..
  61. REGULATION OF DEVELOPMENTAL RENAL HEMODYNAMICS
    Michael Solhaug; Fiscal Year: 2005
    ..Identifying the regulatory relationships between AII and NOS may lead to preventive or therapeutic measures to treat neonatal ARF. ..
  62. Mechanisms of High Flow Induced Vasculopathy
    Elizabeth Jacobs; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  63. ETHANOL ON CALCIUM CHANNELS AND NMDA RECEPTORS
    STEVEN LESLIE; Fiscal Year: 1991
    ..Finally, studies will be conducted to examine the effects of chronic ethanol exposure in adult rats on NMDA- receptor modulation...