Donald M Bers

Summary

Affiliation: Loyola University Medical Center
Country: USA

Publications

  1. ncbi Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure
    Xun Ai
    Department of Medicine, University of Illinois at Chicago, IL 60612, USA
    Circ Res 97:1314-22. 2005
  2. ncbi Cardiac excitation-contraction coupling
    Donald M Bers
    Department of Physiology, Stritch School of Medicine, Loyola Unversity Chicago, IL 60153, USA
    Nature 415:198-205. 2002
  3. ncbi Calcium cycling and signaling in cardiac myocytes
    Donald M Bers
    Department of Physiology and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
    Annu Rev Physiol 70:23-49. 2008
  4. ncbi Intracellular Na+ regulation in cardiac myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    Cardiovasc Res 57:897-912. 2003
  5. ncbi Dynamic imaging in living cells: windows into local signaling
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    Sci STKE 2003:PE13. 2003
  6. ncbi Calcium signaling in cardiac ventricular myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153, USA
    Ann N Y Acad Sci 1047:86-98. 2005
  7. pmc Cardiac ryanodine receptor phosphorylation: target sites and functional consequences
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    Biochem J 396:e1-3. 2006
  8. ncbi Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    Basic Res Cardiol 97:I36-42. 2002
  9. ncbi Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    J Pharmacol Sci 100:315-22. 2006
  10. pmc Going to cAMP just got more complicated
    Donald M Bers
    Dpartment of Physiology, Loyola University, Chicago Maywood, IL, USA
    J Physiol 583:415-6. 2007

Research Grants

Detail Information

Publications98

  1. ncbi Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure
    Xun Ai
    Department of Medicine, University of Illinois at Chicago, IL 60612, USA
    Circ Res 97:1314-22. 2005
    ..Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF...
  2. ncbi Cardiac excitation-contraction coupling
    Donald M Bers
    Department of Physiology, Stritch School of Medicine, Loyola Unversity Chicago, IL 60153, USA
    Nature 415:198-205. 2002
    ..Furthermore, spatial microdomains within the cell are important in localizing the molecular players that orchestrate cardiac function...
  3. ncbi Calcium cycling and signaling in cardiac myocytes
    Donald M Bers
    Department of Physiology and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
    Annu Rev Physiol 70:23-49. 2008
    ..Importantly, although such diverse Ca-dependent regulations occur simultaneously in a cell, the cell can distinguish distinct signals by local Ca or protein complexes and differential Ca signal integration...
  4. ncbi Intracellular Na+ regulation in cardiac myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    Cardiovasc Res 57:897-912. 2003
    ..Thus, the balance of Na+ fluxes in heart cells may be complex, but myocyte Na+ regulation is functionally important and merits focused attention as in this issue...
  5. ncbi Dynamic imaging in living cells: windows into local signaling
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    Sci STKE 2003:PE13. 2003
    ..Complementary approaches useful in studying localized changes in Ca2+ and other second messengers (such as cyclic adenosine monophosphate) are also discussed...
  6. ncbi Calcium signaling in cardiac ventricular myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153, USA
    Ann N Y Acad Sci 1047:86-98. 2005
    ..In this way cells can use Ca signaling in multiple ways that function in spatially and temporally distinct manners...
  7. pmc Cardiac ryanodine receptor phosphorylation: target sites and functional consequences
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    Biochem J 396:e1-3. 2006
    ..This study brings some new answers, but also raises additional new questions that will require further investigation...
  8. ncbi Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure
    Donald M Bers
    Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    Basic Res Cardiol 97:I36-42. 2002
    ..We conclude that NaCaX contributes in major ways to both contractile dysfunction (by reducing SR Ca) and increased propensity for triggered arrhythmias (by increasing I(ti) and DADs)...
  9. ncbi Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    J Pharmacol Sci 100:315-22. 2006
    ..Phospholemman is an important regulator of NKA function (decreasing [Na(+)](i) affinity unless it is phosphorylated). Here we discuss the interplay between Ca(2+) and Na(+) in myocytes from normal and failing hearts...
  10. pmc Going to cAMP just got more complicated
    Donald M Bers
    Dpartment of Physiology, Loyola University, Chicago Maywood, IL, USA
    J Physiol 583:415-6. 2007
  11. ncbi Sarcoplasmic reticulum Ca release in intact ventricular myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    Front Biosci 7:d1697-711. 2002
    ..These issues are discussed in both normal physiological and pathophysiological contexts...
  12. ncbi Macromolecular complexes regulating cardiac ryanodine receptor function
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 37:417-29. 2004
    ..These complexes, and their relative independence emphasizes the importance of thinking about other aspects of very local molecular signaling, analogous to the local control of SR Ca-release at the heart of current (E-C) coupling theory...
  13. ncbi Altered cardiac myocyte Ca regulation in heart failure
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA
    Physiology (Bethesda) 21:380-7. 2006
    ..In heart failure, there are significant alterations in how myocyte Ca is regulated, and these alterations are critical in dictating both contractile dysfunction and certain cardiac arrhythmias that are characteristic of heart failure...
  14. ncbi Na:Ca stoichiometry and cytosolic Ca-dependent activation of NCX in intact cardiomyocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    Ann N Y Acad Sci 1099:326-38. 2007
    ..However, evidence from subcellular and expression systems shows the process to be dynamic, and our observations confirm this to be the case in intact cardiac cells as well...
  15. ncbi Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes
    Donald M Bers
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153 5500, USA
    Ann N Y Acad Sci 1080:165-77. 2006
    ..The lower expression level of more phosphorylated PLM in HF may explain the above dichotomy. Thus, altered Ca(2+) and Na(+) handling contributes to altered contractile function and arrhythmogenesis in HF...
  16. doi Ca2+/calmodulin-dependent protein kinase IIdelta and protein kinase D overexpression reinforce the histone deacetylase 5 redistribution in heart failure
    Julie Bossuyt
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA
    Circ Res 102:695-702. 2008
    ..This may directly contribute to the development and/or maintenance of HF...
  17. pmc Phospholemman-mediated activation of Na/K-ATPase limits [Na]i and inotropic state during beta-adrenergic stimulation in mouse ventricular myocytes
    Sanda Despa
    Department of Physiology, Loyola University Chicago, Maywood, Ill, USA
    Circulation 117:1849-55. 2008
    ..Recent evidence shows that phosphorylation of the NKA-associated small transmembrane protein phospholemman (PLM) mediates beta-adrenergic-induced NKA stimulation...
  18. pmc The inotropic effect of cardioactive glycosides in ventricular myocytes requires Na+-Ca2+ exchanger function
    Julio Altamirano
    Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    J Physiol 575:845-54. 2006
    ..We conclude that the acute inotropic effects of DIG, ACS and OUA (and the effects on RyRs) depend on the presence of Na(+) and a functional NCX in ferret and cat myocytes (rather than alternate Na(+)-independent mechanisms)...
  19. ncbi Voltage dependence of cardiac excitation-contraction coupling: unitary Ca2+ current amplitude and open channel probability
    Julio Altamirano
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, Maywood, IL 60153, USA
    Circ Res 101:590-7. 2007
    ..At very positive V(m), reduced i(Ca) must explain reduced SR Ca2+ release...
  20. ncbi Ca2+/Calmodulin-dependent protein kinase II phosphorylation of ryanodine receptor does affect calcium sparks in mouse ventricular myocytes
    Tao Guo
    Department of Physiology and Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    Circ Res 99:398-406. 2006
    ..Moreover, this may explain the enhanced SR diastolic Ca2+ leak and certain triggered arrhythmias seen in heart failure...
  21. ncbi Myocyte nitric oxide synthase 2 contributes to blunted beta-adrenergic response in failing human hearts by decreasing Ca2+ transients
    Mark T Ziolo
    Department of Physiology, Loyola University Medical Center, Maywood, Ill 60153, USA
    Circulation 109:1886-91. 2004
    ..Here, we examined whether expression of nitric oxide synthase-2 (NOS2, or inducible NOS) contributes to this loss of inotropic reserve in human HF...
  22. ncbi Phospholemman phosphorylation mediates the protein kinase C-dependent effects on Na+/K+ pump function in cardiac myocytes
    Fei Han
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, Maywood, IL 60153, USA
    Circ Res 99:1376-83. 2006
    ..5), respectively), and (3) PDBu and ISO combine to activate NKA in wild-type to the level found in the PLM knockout mouse...
  23. pmc Ca sparks do not explain all ryanodine receptor-mediated SR Ca leak in mouse ventricular myocytes
    Demetrio J Santiago
    Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois, USA
    Biophys J 98:2111-20. 2010
    ..However, we also found that sparks explain approximately half of J(leak). Our strategy unmasks the presence of a subresolution (i.e., nonspark) release of potential physiological relevance...
  24. ncbi Intracellular Na(+) concentration is elevated in heart failure but Na/K pump function is unchanged
    Sanda Despa
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA
    Circulation 105:2543-8. 2002
    ..Intracellular sodium concentration ([Na(+)](i)) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [Na(+)](i)...
  25. pmc A mathematical treatment of integrated Ca dynamics within the ventricular myocyte
    Thomas R Shannon
    Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois, USA
    Biophys J 87:3351-71. 2004
    ..We conclude that this model is more robust than many previously existing models and reproduces many experimental results using parameters based largely on experimental measurements in myocytes...
  26. ncbi Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release
    Lars S Maier
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave, Maywood, Ill 60153, USA
    Circ Res 92:904-11. 2003
    ..We conclude that CaMKIIdeltaC overexpression causes acute modulation of excitation-contraction coupling, which contributes to heart failure...
  27. pmc CaMKII inhibition targeted to the sarcoplasmic reticulum inhibits frequency-dependent acceleration of relaxation and Ca2+ current facilitation
    Eckard Picht
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 42:196-205. 2007
    ..Thus SR-targeted CaMKII inhibition can directly inhibit the activation of SR Ca(2+) uptake, SR Ca(2+) release and I(Ca) by CaMKII, effects which have all been implicated in triggered arrhythmias...
  28. pmc Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman
    Fei Han
    Department of Pathology, Northwestern University, Feinberg School of Chicago, Chicago, Illinois, USA
    Am J Physiol Cell Physiol 297:C699-705. 2009
    ....
  29. ncbi Dynamic regulation of sodium/calcium exchange function in human heart failure
    Christopher R Weber
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill 60153, USA
    Circulation 108:2224-9. 2003
    ..Therefore, changes in NCX function may contribute to abnormal Ca regulation in human HF...
  30. ncbi Biosensors to measure inositol 1,4,5-trisphosphate concentration in living cells with spatiotemporal resolution
    Timothy P Remus
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    J Biol Chem 281:608-16. 2006
    ..These new biosensors allow studying InsP3 dynamics at high temporal and spatial resolution that will be powerful in under-standing InsP3 signaling in intact cells...
  31. ncbi Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations
    Eckard Picht
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, Maywood, IL 60153, USA
    Circ Res 99:740-8. 2006
    ..In this way, diastolic [Ca2+]SR alternans can enhance frequency-induced Ca2+ alternans, even if they initiate by other means...
  32. pmc Local InsP3-dependent perinuclear Ca2+ signaling in cardiac myocyte excitation-transcription coupling
    Xu Wu
    Loyola University Chicago, Chicago, Illinois 60153, USA
    J Clin Invest 116:675-82. 2006
    ..Thus, myocytes can distinguish simultaneous local and global Ca2+ signals involved in contractile activation from those targeting gene expression...
  33. pmc Partial inhibition of sarcoplasmic reticulum ca release evokes long-lasting ca release events in ventricular myocytes: role of luminal ca in termination of ca release
    Aleksey V Zima
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
    Biophys J 94:1867-79. 2008
    ..Eventually, these events terminate by luminal Ca-independent mechanisms, such as inactivation, adaptation, or stochastic attrition...
  34. pmc Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger
    Kenneth S Ginsburg
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    J Physiol 556:463-80. 2004
    ..The increased amount of SR Ca(2+) release normally seen with ISO depends primarily on increased I(Ca) trigger and SR Ca(2+) load, whereas faster release kinetics may be the main result of RyR phosphorylation...
  35. ncbi Dynamic changes in free Ca-calmodulin levels in adult cardiac myocytes
    Lars S Maier
    Department of Physiology, Stritch School of Medicine Loyola University, Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 41:451-8. 2006
    ..Our results indicate that there are dynamic changes in free Ca-CaM levels (a phasic component tracking [Ca]i) as well as system memory that integrates the [Ca]i signals (a tonic component)...
  36. ncbi Cardiac submembrane [Na+] transients sensed by Na+-Ca2+ exchange current
    Christopher R Weber
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Ave, Maywood, Ill 60153, USA
    Circ Res 92:950-2. 2003
    ..This suggests that INa effects on excitation-contraction coupling (via outward INCX) are minimal and limited to early during the action potential. However, local Delta[Na+]sm during INa may be 60 times higher than bulk Delta[Na+]i...
  37. pmc Phospholamban oligomerization, quaternary structure, and sarco(endo)plasmic reticulum calcium ATPase binding measured by fluorescence resonance energy transfer in living cells
    Eileen M Kelly
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    J Biol Chem 283:12202-11. 2008
    ..Truncation of the transmembrane domain by L39Stop mutation prevents anchoring of the protein in the membrane, greatly reducing PLB binding to itself or its regulatory target, SERCA...
  38. pmc Differential integration of Ca2+-calmodulin signal in intact ventricular myocytes at low and high affinity Ca2+-calmodulin targets
    Qiujing Song
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    J Biol Chem 283:31531-40. 2008
    ....
  39. ncbi Quantitative assessment of the SR Ca2+ leak-load relationship
    Thomas R Shannon
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA
    Circ Res 91:594-600. 2002
    ....
  40. ncbi Isoproterenol does not enhance Ca-dependent Na/Ca exchange current in intact rabbit ventricular myocytes
    Kenneth S Ginsburg
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 39:972-81. 2005
    ..However, such effects are likely to be either minor (vs. other PKA actions on myocyte Ca handling) or indirect, such as secondary effects dependent on altered local [Ca](i) and [Na](i)...
  41. ncbi Protein kinase A phosphorylation of the ryanodine receptor does not affect calcium sparks in mouse ventricular myocytes
    Yanxia Li
    Department of Physiology and Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill 60153, USA
    Circ Res 90:309-16. 2002
    ..Moreover, the data provide compelling evidence that elevated intra-SR [Ca2+] increases RyR gating independent of cytosolic [Ca2+] (which was clamped)...
  42. pmc Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca(2+)-calmodulin-dependent protein kinase II
    Jerry Curran
    Rush University, Chicago, IL, USA
    J Mol Cell Cardiol 49:25-32. 2010
    ..Treatment with ISO plus KN93 completely abolished this effect. The evidence suggests the ISO-dependent increase in SCaW activity in both healthy and failing myocytes is CaMKII-dependent, implicating CaMKII in arrhythmogenesis...
  43. pmc Ryanodine receptor phosphorylation at Serine 2030, 2808 and 2814 in rat cardiomyocytes
    Sabine Huke
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA Department of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Biochem Biophys Res Commun 376:80-5. 2008
    ..Phosphatase 1 appears to be the main phosphatase dephosphorylating S2808/S2814, but phosphatase 2a may also dephosphorylate S2814. RyR phosphorylation is complex, but important in understanding RyR functional modulation...
  44. pmc Role of phospholemman phosphorylation sites in mediating kinase-dependent regulation of the Na+-K+-ATPase
    Fei Han
    Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
    Am J Physiol Cell Physiol 299:C1363-9. 2010
    ..We conclude that PLM phosphorylation at either Ser63 or Ser68 is both necessary and sufficient for completely relieving the PLM-induced NKA inhibition...
  45. ncbi Adenoviral gene transfer of mutant phospholamban rescues contractile dysfunction in failing rabbit myocytes with relatively preserved SERCA function
    Mark T Ziolo
    Department of Physiology, Loyola University Chicago, Maywood, Ill, USA
    Circ Res 96:815-7. 2005
    ..This approach could enhance contractile function in failing hearts of various etiologies, even here where reduced SERCA activity is not the main dysfunction...
  46. ncbi Calcium influx via I(NCX) is favored in failing human ventricular myocytes
    Christopher R Weber
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    Ann N Y Acad Sci 976:478-9. 2002
  47. ncbi Phospholemman phosphorylation alters its fluorescence resonance energy transfer with the Na/K-ATPase pump
    Julie Bossuyt
    Department of Physiology, Loyola University Chicago, 2160 S First Avenue, Maywood, IL 60153, USA
    J Biol Chem 281:32765-73. 2006
    ..We conclude that phospholemman and Na/K-pump are in very close proximity (FRET occurs) and that phospholemman phosphorylation alters the interaction of Na/K-pump and phospholemman...
  48. ncbi SparkMaster: automated calcium spark analysis with ImageJ
    Eckard Picht
    Dept of Physiology, Loyola Univ Chicago, Stritch School of Medicine, 2160 South First Ave, Maywood, IL 60153, USA
    Am J Physiol Cell Physiol 293:C1073-81. 2007
    ..We found that SparkMaster provides a reliable, easy to use, and fast way of analyzing Ca sparks in a wide variety of experimental conditions...
  49. ncbi Sarcoplasmic reticulum and nuclear envelope are one highly interconnected Ca2+ store throughout cardiac myocyte
    Xu Wu
    Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153, USA
    Circ Res 99:283-91. 2006
    ..This rapid luminal communication may maintain homogeneously high luminal [Ca(2+)], ensuring a robust and uniform driving force for local Ca(2+) release events from either SR or NucEn...
  50. ncbi Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes
    Sanda Despa
    Dept of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Ave, Maywood, IL 60153, USA
    Am J Physiol Cell Physiol 293:C321-7. 2007
    ..The functional density of NKA-alpha2 is approximately 4.5 times higher in the T-tubules vs. ESL, whereas NKA-alpha1 is almost uniformly distributed between the TT and ESL...
  51. ncbi Ca2+ scraps: local depletions of free [Ca2+] in cardiac sarcoplasmic reticulum during contractions leave substantial Ca2+ reserve
    Thomas R Shannon
    Department of Physiology, Loyola University Chicago, Maywood, Ill, USA
    Circ Res 93:40-5. 2003
    ..These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca2+ store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure...
  52. ncbi Modulation of contractility in failing human myocytes by reverse-mode Na/Ca exchange
    Valentino Piacentino
    Department of Physiology, Temple University, Philadelphia, Pennsylvania 19140, USA
    Ann N Y Acad Sci 976:466-71. 2002
    ..We hypothesize that this increased Ca influx can explain the slowed decay and impaired relaxation of failing human ventricular myocytes...
  53. ncbi Expression and phosphorylation of the na-pump regulatory subunit phospholemman in heart failure
    Julie Bossuyt
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA
    Circ Res 97:558-65. 2005
    ..So reduced Na/K-ATPase expression in HF may be functionally offset by lower inhibition by PLM (because of reduced PLM expression and higher PLM phosphorylation)...
  54. ncbi Modeling the isolated cardiac myocyte
    Jose L Puglisi
    Department of Physiology, Loyola University Chicago, 2160 S First Avenue, Maywood, IL 60153, USA
    Prog Biophys Mol Biol 85:163-78. 2004
    ..The contribution of the computer modeler to their respective biological fields will be more successful and enduring if modelers devote sufficient time to implement their equations into a model with user-friendly characteristics...
  55. pmc Temporal dissociation of frequency-dependent acceleration of relaxation and protein phosphorylation by CaMKII
    Sabine Huke
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave, Maywood, IL 60153 5500, USA
    J Mol Cell Cardiol 42:590-9. 2007
    ....
  56. ncbi Na/Ca exchange function in intact ventricular myocytes
    Donald M Bers
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    Ann N Y Acad Sci 976:500-12. 2002
    ..Our simulations suggest that NCX current is outward for less than approximately 10 ms at the beginning of the action potential...
  57. ncbi Intra-sarcoplasmic reticulum free [Ca2+] and buffering in arrhythmogenic failing rabbit heart
    Tao Guo
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    Circ Res 101:802-10. 2007
    ..We conclude that low total SR Ca2+ content in HF, and reduced SR Ca2+ release, is attributable to reduced [Ca2+]SR, not to alterations in SR volume or Ca2+ buffering capacity...
  58. ncbi Phospholemman-phosphorylation mediates the beta-adrenergic effects on Na/K pump function in cardiac myocytes
    Sanda Despa
    Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA
    Circ Res 97:252-9. 2005
    ..We conclude that PLM modulates the NKA function in a manner similar to the way phospholamban affects the related SR Ca-ATPase (inhibition of transport substrate affinity, that is relieved by phosphorylation)...
  59. pmc Na/K pump current and [Na](i) in rabbit ventricular myocytes: local [Na](i) depletion and Na buffering
    Sanda Despa
    Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    Biophys J 84:4157-66. 2003
    ..I(pump) integrals and [Na](i) decline were used to estimate intracellular Na buffering, which is slight (1.39 +/- 0.09)...
  60. pmc Phosphomimetic mutations enhance oligomerization of phospholemman and modulate its interaction with the Na/K-ATPase
    Qiujing Song
    Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA
    J Biol Chem 286:9120-6. 2011
    ..We conclude that phosphorylation of PLM increases its oligomerization into tetramers, decreases its binding to NKA, and alters the structures of both the tetramer and NKA regulatory complex...
  61. ncbi Effect of intracellular Ca2+ and action potential duration on L-type Ca2+ channel inactivation and recovery from inactivation in rabbit cardiac myocytes
    Julio Altamirano
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave, Maywood, IL 60153, USA
    Am J Physiol Heart Circ Physiol 293:H563-73. 2007
    ..We conclude that long APD and slower [Ca(2+)](i) decline lead to cumulative inactivation limiting I(Ca) at high heart rates and might contribute to the negative FFR in HF, independent of altered Ca(2+) channel properties...
  62. pmc Free and bound intracellular calmodulin measurements in cardiac myocytes
    Xu Wu
    Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153, United States
    Cell Calcium 41:353-64. 2007
    ..Bound CaM is relatively concentrated at Z-lines at rest but translocates significantly to the nucleus upon elevation of [Ca2+]i, which may influence activation of different targets and cellular functions...
  63. pmc Ca²+ spark-dependent and -independent sarcoplasmic reticulum Ca²+ leak in normal and failing rabbit ventricular myocytes
    Aleksey V Zima
    Department of Cell and Molecular Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    J Physiol 588:4743-57. 2010
    ..These results show that RyRs are the main, but not sole contributor to SR Ca²(+) leak. RyR-mediated leak occurs in part as Ca²(+) sparks, but there is clearly RyR-mediated but Ca²(+) sparks independent leak...
  64. ncbi Na(+)-Ca(2+) exchange current and submembrane [Ca(2+)] during the cardiac action potential
    Christopher R Weber
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA
    Circ Res 90:182-9. 2002
    ..The early rise in [Ca(2+)](sm) causes I(NCX) to be inward for the majority of the AP. Thus, little Ca(2+) influx via NCX is expected under physiological conditions, but this can differ among species and in pathophysiological conditions...
  65. ncbi Frequency-dependent acceleration of relaxation in the heart depends on CaMKII, but not phospholamban
    Jaime DeSantiago
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 34:975-84. 2002
    ..We conclude that FDAR results mainly from CaMKII-dependent stimulation of SR Ca transport, but does not require phospholamban...
  66. pmc Phorbol ester and endothelin-1 alter functional expression of Na+/Ca2+ exchange, K+, and Ca2+ currents in cultured neonatal rat myocytes
    Jose L Puglisi
    Cardiovascular Institute and Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
    Am J Physiol Heart Circ Physiol 300:H617-26. 2011
    ..We conclude that chronic PMA or ET-1 exposure in cultured NRVMs causes altered functional expression of cardiac ion currents, which mimic electrophysiological changes seen in whole animal and human hypertrophy and heart failure...
  67. pmc Na/K pump-induced [Na](i) gradients in rat ventricular myocytes measured with two-photon microscopy
    Sanda Despa
    Department of Physiology, Loyola University Chicago, Maywood, Illinois, USA
    Biophys J 87:1360-8. 2004
    ..A simple diffusion model indicated that such gradients require a Na diffusion coefficient of 10-12 microm(2)/s, significantly lower than in aqueous solutions...
  68. pmc Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes
    Sanda Despa
    Department of Physiology and Cardiovascular Institute, Loyola University Chicago, Maywood, IL 60153, USA
    J Physiol 539:133-43. 2002
    ..We conclude that resting [Na+]i is higher in rat than in rabbit, that this is caused by higher resting Na+ influx in rat and that a higher Na+,K+-ATPase pumping rate in rat is a consequence of the higher [Na+]i...
  69. ncbi Importance of small heat shock protein 20 (hsp20) C-terminal extension in cardioprotection
    Emir Islamovic
    Loyola University Medical Center, Department of Physiology and Cardiovascular Institute, 2160 S First Ave Bldg 110 Rm 5227, Maywood, IL 60153, USA
    J Mol Cell Cardiol 42:862-9. 2007
    ..Hsp20 renders this protection through its C-terminal extension protein domain, while this part of the protein is not involved in the Hsp20 ability to increase both calcium transients and cell contraction...
  70. ncbi Pulmonary arterial hypertension
    Jose Luis Puglisi
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 S First Avenue, Maywood, IL 60130, USA
    Compr Ther 33:231-6. 2007
    ..Better recognition of primary pulmonary hypertension can produce better treatment by comprehensive therapists...
  71. ncbi Calcium, calmodulin, and calcium-calmodulin kinase II: heartbeat to heartbeat and beyond
    Lars S Maier
    Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Chicago, IL 60153, USA
    J Mol Cell Cardiol 34:919-39. 2002
    ..Here we review the classical role of Ca in E-C coupling and extend this view to the role of the Ca-dependent proteins CaM and CaMKII in modulating E-C coupling and their contribution to E-T coupling...
  72. ncbi Sudden unexpected death
    W H Wehrmacher
    Department of Pathology, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60513, USA
    Compr Ther 31:176-80. 2005
    ..Many cases could be prevented if they were anticipated through means of a better awareness among the medical community, new therapies based on early genetic screening, or corrected by countershock...
  73. ncbi Cardiac type 2 inositol 1,4,5-trisphosphate receptor: interaction and modulation by calcium/calmodulin-dependent protein kinase II
    Dan J Bare
    Department of Physiology and Cardiovascular Institute, Loyola University Chicago, Maywood, Illinois 60153, USA
    J Biol Chem 280:15912-20. 2005
    ....
  74. pmc Modulation of SR Ca release by luminal Ca and calsequestrin in cardiac myocytes: effects of CASQ2 mutations linked to sudden cardiac death
    Dmitry Terentyev
    Department of Physiology, Dorothy M Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio 43210 1252, USA
    Biophys J 95:2037-48. 2008
    ..Furthermore, two CPVT-inducing CASQ2 mutations, which cause mechanistically different defects in CASQ2 and RyR2 function, lead to increased diastolic SR Ca release events and exhibit a similar CPVT disease phenotype...
  75. ncbi Integrated Ca2+ management in cardiac myocytes
    Thomas R Shannon
    Deparment of Physiology and Cardiovascular Institute, Loyola University Chicago, Maywood, IL 60153, USA
    Ann N Y Acad Sci 1015:28-38. 2004
    ....
  76. ncbi Na/Ca exchange in heart failure: contractile dysfunction and arrhythmogenesis
    Steven M Pogwizd
    Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    Ann N Y Acad Sci 976:454-65. 2002
    ..Therapeutic approaches to the treatment of HF will need to balance increasing SR Ca load with the arrhythmogenic effects of SR Ca overload that involve activation of I(ti) carried by Na/Ca exchanger...
  77. pmc Termination of cardiac Ca2+ sparks: role of intra-SR [Ca2+], release flux, and intra-SR Ca2+ diffusion
    Aleksey V Zima
    Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA
    Circ Res 103:e105-15. 2008
    ..Thus, reliable SR Ca(2+) release termination depends on tight RyR regulation by [Ca(2+)](SR)...
  78. ncbi Histidine-rich Ca binding protein: a regulator of sarcoplasmic reticulum calcium sequestration and cardiac function
    Kimberly N Gregory
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267 0575, USA
    J Mol Cell Cardiol 40:653-65. 2006
    ..Collectively, these data suggest that HRC may be an integral regulatory protein involved in cardiac muscle SR Ca uptake and Ca homeostasis...
  79. pmc Arrhythmogenic effects of beta2-adrenergic stimulation in the failing heart are attributable to enhanced sarcoplasmic reticulum Ca load
    Jaime DeSantiago
    Department of Pharmacology, University of California Davis, Davis, CA, USA
    Circ Res 102:1389-97. 2008
    ..Thus, beta(2)-AR stimulation is arrhythmogenic in HF, mediated by SR Ca overload-induced spontaneous SR Ca release and aftercontractions...
  80. ncbi Targeted inhibition of sarcoplasmic reticulum CaMKII activity results in alterations of Ca2+ homeostasis and cardiac contractility
    Yong Ji
    Dept of Genome Science, Univ of Cincinnati College of Medicine, 2180 E Galbraith Road, Cincinnati, OH 45237 0505, USA
    Am J Physiol Heart Circ Physiol 290:H599-606. 2006
    ..This study demonstrates that inhibition of SR CaMKII activity at the LSR results in alterations in cardiac contractility and Ca2+ handling in TG hearts...
  81. pmc Regulation of cardiac sarcoplasmic reticulum Ca release by luminal [Ca] and altered gating assessed with a mathematical model
    Thomas R Shannon
    Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612, USA
    Biophys J 89:4096-110. 2005
    ..We conclude that RyR regulation may play a role in preventing arrhythmias in healthy myocytes but that the same regulation may have the opposite effect in chronic heart failure...
  82. ncbi Cellular basis of abnormal calcium transients of failing human ventricular myocytes
    Valentino Piacentino
    Molecular and Cellular Cardiology Laboratories, Cardiovascular Research Group, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Circ Res 92:651-8. 2003
    ..These changes can explain the defective Ca2+ transients of the failing human ventricular myocyte...
  83. pmc Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels
    Stefan Wagner
    Department of Cardiology and Pneumology, Georg August University Gottingen, Gottingen, Germany
    J Clin Invest 116:3127-38. 2006
    ..In mice, enhanced CaMKIIdelta(C) activity predisposed to VT. Thus, CaMKII-dependent regulation of Na(+) channel function may contribute to arrhythmogenesis in HF...
  84. ncbi Chronic SR Ca2+-ATPase inhibition causes adaptive changes in cellular Ca2+ transport
    Angela G Brittsan
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670575, Cincinnati, Ohio 45267 0575, USA
    Circ Res 92:769-76. 2003
    ..This ICa modulation may partly compensate for the loss in SERCA2a responsiveness and thereby partially normalize beta-adrenergic inotropy in DM phospholamban mice...
  85. ncbi Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure
    Thomas R Shannon
    Department of Molecular Biophysics and Physiology, Rush University, 1750 W Harrison Ave, Chicago, Ill 60612, USA
    Circ Res 93:592-4. 2003
    ..We conclude that increased diastolic SR Ca2+ leak in HF may contribute to reductions in SR Ca2+ content, but changes in NCX in this HF model have more impact on [Ca2+]SRT...
  86. ncbi Sarcoplasmic reticulum Ca2+ and heart failure: roles of diastolic leak and Ca2+ transport
    Donald M Bers
    Circ Res 93:487-90. 2003
  87. ncbi Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase
    Jerald Curran
    Rush University Medical Center, Chicago, IL 60611, USA
    Circ Res 100:391-8. 2007
    ..The results suggest that beta-AR stimulation enhances diastolic SR Ca leak in a manner that is (1) CaMKII dependent, (2) not protein kinase A dependent, and 3) not dependent on bulk [Ca](i)...
  88. ncbi The beat goes on: diastolic noise that just won't quit
    Donald M Bers
    Circ Res 99:921-3. 2006
  89. ncbi Impaired relaxation in transgenic mice overexpressing junctin
    Uwe Kirchhefer
    Institut fur Pharmakologie und Toxikologie, Westfalische Wilhelms Universitat, Domagkstrasse 12, 48149 Munster, Germany
    Cardiovasc Res 59:369-79. 2003
    ..Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin...
  90. ncbi Cardiac pacemaking: I(f) vs. Ca(2+), is it really that simple?
    Stephen L Lipsius
    J Mol Cell Cardiol 35:891-3. 2003
  91. ncbi Excessive sarcoplasmic/endoplasmic reticulum Ca2+-ATPase expression causes increased sarcoplasmic reticulum Ca2+ uptake but decreases myocyte shortening
    Nils Teucher
    Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany
    Circulation 110:3553-9. 2004
    ..We investigated the effects of different levels of SERCA1a expression on contractility and Ca2+ cycling. We tested whether increased SERCA1a expression levels enhance myocyte contractility in a gene-dose-dependent manner...
  92. pmc Modelling calcium microdomains using homogenisation
    Erin R Higgins
    Department of Mathematics, University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Theor Biol 247:623-44. 2007
    ..Our method is illustrated by a simple model of the diadic cleft of a cardiac half-sarcomere...
  93. pmc Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes
    Rosana A Bassani
    Centro de Engenharia Biomédica, Universidade Estadual de Campinas, 13084 971 Campinas, SP, Brazil
    J Physiol 559:593-609. 2004
    ....
  94. ncbi The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure
    Tong Zhang
    Department of Pharmacology, University of California, San Diego, 9500 Gilman Dr, La Jolla, Calif 92093 0636, USA
    Circ Res 92:912-9. 2003
    ....
  95. pmc Simulation of Ca-calmodulin-dependent protein kinase II on rabbit ventricular myocyte ion currents and action potentials
    Eleonora Grandi
    Biomedical Engineering Laboratory, Department of Electronics, Computer Science and Systems, University of Bologna, Bologna, Italy
    Biophys J 93:3835-47. 2007
    ..This provides a useful initial framework to consider pathways by which CaMKII may contribute to arrhythmogenesis...
  96. ncbi Differential distribution and regulation of mouse cardiac Na+/K+-ATPase alpha1 and alpha2 subunits in T-tubule and surface sarcolemmal membranes
    Roger G Berry
    Cardiac Physiology, King s College London, The Rayne Institute, St Thomas Hospital, London SE1 7EH, UK
    Cardiovasc Res 73:92-100. 2007
    ..The subcellular distribution of these isoforms in T-tubule and surface sarcolemmal (SSL) membranes and their regulation by cAMP-dependent protein kinase (PKA) is unclear...
  97. ncbi Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent
    Dirk von Lewinski
    Department of Cardiology and Pneumology, Georg August University, Robert Koch Str 40, 37075, Gottingen, Germany
    Cardiovasc Res 57:1052-61. 2003
    ..Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium...
  98. ncbi Increased sarcoplasmic reticulum calcium leak but unaltered contractility by acute CaMKII overexpression in isolated rabbit cardiac myocytes
    Michael Kohlhaas
    Abteilung Kardiologie and Pneumologie Herzzentrum, Georg August Universitat Gottingen, Germany
    Circ Res 98:235-44. 2006
    ..We conclude that this is attributable to concomitant enhancement of fractional SR Ca2+ release in CaMKIIdeltaC myocytes (ie, CaMKII-dependent enhancement of RyR Ca2+ sensitivity during diastole and systole) and increased ICa...

Research Grants1

  1. IONIC CONTROL OF CARDIAC MUSCLE CONTRACTION: EC COUPLING
    Donald Bers; Fiscal Year: 2007
    ..This work will greatly increase fundamental understanding of key cardiac Ca transport systems in the intact cellular environment under physiological conditions. ..