Heart, Lung and Circulation
Volume 18, Issue 1 , Pages 3-10 , February 2009

The L-type Ca2+ Channel as a Potential Mediator of Pathology During Alterations in Cellular Redox State

  • Livia C. Hool, PhD

      Affiliations

    • Corresponding Author InformationCorrespondence address: Physiology M311, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia, 6009, Australia. Tel.: +61 8 6488 3307; fax: +61 8 6488 1025.

References 

  1. Soldatov NM. Genomic structure of human L-type Ca2+ channel. Genomics. 1994;22:77–87
  2. Dolphin AC. Beta subunits of voltage-gated calcium channels. J Bioenerg Biomembr. 2003;35:599–620
  3. Kobrinsky E, Tiwari S, Maltsev VA, Harry JB, Lakatta E, Abernethy DR, et al. Differential role of the alpha1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits, and Ca2+ ions. J Biol Chem. 2005;280:12474–12485
  4. Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F. Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci. 1999;19:684–691
  5. Bers DM. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol. 2008;70:23–49
  6. Tomida T, Hirose K, Takizawa A, Shibasaki F, Iino M. NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation. EMBO J. 2003;22:3825–3832
  7. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?. Br J Pharmacol. 2004;142:231–255
  8. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol. 2000;279:L1005–L1028
  9. Antunes F, Cadenas E. Estimation of H2O2 gradients across biomembranes. FEBS Lett. 2000;475:121–126
  10. Hurd TR, Filipovska A, Costa NJ, Dahm CC, Murphy MP. Disulphide formation on mitochondrial protein thiols. Biochem Soc Trans. 2005;33:1390–1393
  11. Oshino N, Chance B, Sies H, Bucher T. The role of H2O2 generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors. Arch Biochem Biophys. 1973;154:117–131
  12. Stone JR, Yang S. Hydrogen peroxide: a signaling messenger. Antiox Redox Sig. 2006;8:243–270
  13. Leto TL, Geiszt M. Role of Nox family NADPH oxidases in host defense. Antiox Redox Sig. 2006;8:1549–1561
  14. Behe P, Segal AW. The function of the NADPH oxidase of phagocytes, and its relationship to other NOXs. Biochem Soc Trans. 2007;35:1100–1103
  15. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000;86:494–501
  16. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation Contribution to alterations of vasomotor tone. J Clin Invest. 1996;97:1916–1923
  17. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, et al. Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension. 1998;32:488–495
  18. Byrne JA, Grieve DJ, Bendall JK, Li JM, Gove C, Lambeth JD, et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res. 2003;93:802–805
  19. Li JM, Gall NP, Grieve DJ, Chen M, Shah AM. Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension. 2002;40:477–484
  20. Kang SM, Lim S, Song H, Chang W, Lee S, Bae SM, et al. Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes. Eur J Pharmacol. 2006;535:212–219
  21. Stull LB, Leppo MK, Szweda L, Gao WD, Marban E. Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. Circ Res. 2004;95:1005–1011
  22. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol. 2002;282:C227–C241
  23. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the pathogenesis of hypertension?. Proc Nat Acad Sci USA. 1991;88:10045–10048
  24. White CR, Brock TA, Chang LY, Crapo J, Briscoe P, Ku D, et al. Superoxide and peroxynitrite in atherosclerosis. Proc Nat Acad Sci USA. 1994;91:1044–1048
  25. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335–344
  26. Turrens JF. Superoxide production by the mitochondrial respiratory chain. Bioscience Reports. 1997;17:3–8
  27. Starkov AA, Fiskum G. Regulation of brain mitochondrial H2O2 production by membrane potential and NAD(P)H redox state. J Neurochem. 2003;86:1101–1107
  28. Korshunov SS, Skulachev VP, Starkov AA. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. 1997;416:15–18
  29. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 2005;70:200–214
  30. Wolin MS. Interactions of oxidants with vascular signaling systems. Arter Thromb Vasc Biol. 2000;20:1430–1442
  31. Halliwell B. The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis. 1993;23:118–126
  32. Sabri A, Hughie HH, Lucchesi PA. Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. Antiox Redox Signal. 2003;5:731–740
  33. Khan AU, Wilson T. Reactive oxygen species as cellular messengers. Chem Biol. 1995;2:437–445
  34. Hool LC. Hypoxia increases the sensitivity of the L-type Ca(2+) current to beta-adrenergic receptor stimulation via a C2 region-containing protein kinase C isoform. Circ Res. 2000;87:1164–1171
  35. Hool LC. Hypoxia alters the sensitivity of the L-type Ca(2+) channel to alpha-adrenergic receptor stimulation in the presence of beta-adrenergic receptor stimulation. Circ Res. 2001;88:1036–1043
  36. Casey TM, Pakay JL, Guppy M, Arthur PG. Hypoxia causes downregulation of protein and RNA synthesis in noncontracting Mammalian cardiomyocytes. Circ Res. 2002;90:777–783
  37. Hool LC, Di Maria CA, Viola HM, Arthur PG. Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca2+ channel function during acute hypoxia. Cardiovasc Res. 2005;67:624–635
  38. Archer SL, Reeve HL, Michelakis E, Puttagunta L, Waite R, Nelson DP, et al. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc Nat Acad Sci USA. 1999;96:7944–7949
  39. Archer SL, Weir EK, Reeve HL, Michelakis E. Molecular identification of O2 sensors and O2-sensitive potassium channels in the pulmonary circulation. Adv Exp Med Biol. 2000;475:219–240
  40. O’Kelly I, Peers C, Kemp PJ. NADPH oxidase does not account fully for O2-sensing in model airway chemoreceptor cells. Biochem Biophys Res Commun. 2001;283:1131–1134
  41. Hool LC, Arthur PG. Decreasing cellular hydrogen peroxide with catalase mimics the effects of hypoxia on the sensitivity of the L-type Ca2+ channel to beta-adrenergic receptor stimulation in cardiac myocytes. Circ Res. 2002;91:601–609
  42. Smani T, Hernandez A, Urena J, Castellano AG, Franco-Obregon A, Ordonez A, et al. Reduction of Ca(2+) channel activity by hypoxia in human and porcine coronary myocytes. Cardiovasc Res. 2002;53:97–104
  43. Fearon IM, Palmer AC, Balmforth AJ, Ball SG, Mikala G, Schwartz A, et al. Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type Ca2+ channel. J Physiol. 1997;500:551–556
  44. Fearon IM, Palmer AC, Balmforth AJ, Ball SG, Varadi G, Peers C. Modulation of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by redox agents and hypoxia. J Physiol. 1999;514:629–637
  45. Fearon IM, Varadi G, Koch SE, Isaacsohn I, Ball SG, Peers C. Splice variants reveal the region involved in oxygen sensing by recombinant human L-type Ca2+ channels. Circ Res. 2000;87:537–539
  46. Yamaoka K, Yakehiro M, Yuki T, Fujii H, Seyama I. Effect of sulfhydryl reagents on the regulatory system of the L-type Ca channel in frog ventricular myocytes. Pflugers Arch. 2000;440:207–215
  47. Viola HM, Arthur PG, Hool LC. A transient exposure to hydrogen peroxide causes an increase in mitochondrial-derived superoxide as a result of sustained alteration in L-type Ca2+ channel function in the absence of apoptosis in ventricular myocytes. Circ Res. 2007;100:1036–1044
  48. Campbell DL, Stamler JS, Strauss HC. Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols. J Gen Physiol. 1996;108:277–293
  49. Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993;364:626–632
  50. Gilbert HF. Molecular and cellular aspects of thiol-disulfide exchange. Adv Enzymol Relat Areas Mol Biol. 1990;63:69–172
  51. Carmeliet E. Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Physiol Rev. 1999;79:917–1017
  52. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells [Review] [1868 refs]. Physiol Rev. 1994;74:365–507
  53. Tanskanen AJ, Greenstein JL, O’Rourke B, Winslow RL. The role of stochastic and modal gating of cardiac L-type Ca2+ channels on early after-depolarizations. Biophys J. 2005;88:85–95
  54. El-Sherif N. Mechanism of ventricular arrhythmias in the long QT syndrome: on hermeneutics. J Cardiovasc Electrophysiol. 2001;12:973–976
  55. Sims C, Reisenweber S, Viswanathan PC, Choi BR, Walker WH, Salama G. Sex, age, and regional differences in L-type calcium current are important determinants of arrhythmia phenotype in rabbit hearts with drug-induced long QT type 2. Circ Res. 2008;102:e86–100
  56. January CT, Riddle JM, Salata JJ. A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644. Circ Res. 1988;62:563–571
  57. January CT, Riddle JM. Early afterdepolarizations: mechanism of induction and block A role for L-type Ca2+ current. Circ Res. 1989;64:977–990
  58. Marban E, Robinson SW, Wier WG. Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle. J Clin Invest. 1986;78:1185–1192
  59. Yamada M, Ohta K, Niwa A, Tsujino N, Nakada T, Hirose M. Contribution of L-type Ca2+ channels to early afterdepolarizations induced by I Kr and I Ks channel suppression in guinea pig ventricular myocytes. J Membr Biol. 2008;222:151–166
  60. Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Ann Rev Cell Dev Biol. 2000;16:521–555
  61. Dzhura I, Wu Y, Colbran RJ, Balser JR, Anderson ME. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol. 2000;2:173–177
  62. Volders PG, Kulcsar A, Vos MA, Sipido KR, Wellens HJ, Lazzara R, et al. Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res. 1997;34:348–359
  63. De Ferrari GM, Viola MC, D’Amato E, Antolini R, Forti S. Distinct patterns of calcium transients during early and delayed afterdepolarizations induced by isoproterenol in ventricular myocytes. Circulation. 1995;91:2510–2515
  64. Wu Y, Temple J, Zhang R, Dzhura I, Zhang W, Trimble R, et al. Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophy. Circulation. 2002;106:1288–1293
  65. Mazur A, Roden DM, Anderson ME. Systemic administration of calmodulin antagonist W-7 or protein kinase A inhibitor H-8 prevents torsade de pointes in rabbits. Circulation. 1999;100:2437–2442
  66. Thomas G, Killeen MJ, Grace AA, Huang CL. Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in DeltaKPQ Scn5a murine hearts modelling human long QT 3 syndrome. Acta Physiol (Oxf). 2008;192:505–517
  67. Gallacher DJ, Van de Water A, van der Linde H, Hermans AN, Lu HR, Towart R, et al. In vivo mechanisms precipitating torsades de pointes in a canine model of drug-induced long-QT1 syndrome. Cardiovasc Res. 2007;76:247–256
  68. Dorian P. Antiarrhythmic action of beta-blockers: potential mechanisms. J Cardiovasc Pharm Ther. 2005;10(Suppl. 1):S15–22
  69. Berridge MJ. Remodelling Ca2+ signalling systems and cardiac hypertrophy. Biochem Soc Trans. 2006;34:228–231
  70. Mondry A, Swynghedauw B. Biological adaptation of the myocardium to chronic mechanical overload. Molecular determinants of the autonomic nervous system. Eur Heart J. 1995;16(Suppl. I):64–73
  71. Wilkins BJ, Molkentin JD. Calcineurin and cardiac hypertrophy: where have we been? Where are we going?. J Physiol. 2002;541:1–8
  72. Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol. 2003;65:45–79
  73. Balke CW, Shorofsky SR. Alterations in calcium handling in cardiac hypertrophy and heart failure. Cardiovasc Res. 1998;37:290–299
  74. Wilkins BJ, Molkentin JD. Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun. 2004;322:1178–1191
  75. van Empel VP, De Windt LJ. Myocyte hypertrophy and apoptosis: a balancing act. Cardiovasc Res. 2004;63:487–499
  76. Ruwhof C, van der Laarse A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res. 2000;47:23–37
  77. Dorn GW, Force T. Protein kinase cascades in the regulation of cardiac hypertrophy. J Clin Invest. 2005;115:527–537
  78. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93:215–228
  79. McKinsey TA. Derepression of pathological cardiac genes by members of the CaM kinase superfamily. Cardiovasc Res. 2007;73:667–677
  80. Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature. 1997;386:855–858
  81. Sucharov CC, Mariner PD, Nunley KR, Long C, Leinwand L, Bristow MR. A beta1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction. Am J Physiol. 2006;291:H1299–1308
  82. Zobel C, Rana OR, Saygili E, Bolck B, Diedrichs H, Reuter H, et al. Mechanisms of Ca2+-dependent calcineurin activation in mechanical stretch-induced hypertrophy. Cardiology. 2007;107:281–290
  83. Bodi I, Muth JN, Hahn HS, Petrashevskaya NN, Rubio M, Koch SE, et al. Electrical remodeling in hearts from a calcium-dependent mouse model of hypertrophy and failure: complex nature of K+ current changes and action potential duration. J Am Coll Cardiol. 2003;41:1611–1622
  84. Zou Y, Yamazaki T, Nakagawa K, Yamada H, Iriguchi N, Toko H, et al. Continuous blockade of L-type Ca2+ channels suppresses activation of calcineurin and development of cardiac hypertrophy in spontaneously hypertensive rats. Hypertens Res. 2002;25:117–124
  85. Murata M, Cingolani E, McDonald AD, Donahue JK, Marban E. Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart. Circ Res. 2004;95:398–405
  86. Cingolani E, Ramirez Correa GA, Kizana E, Murata M, Cho HC, Marban E. Gene therapy to inhibit the calcium channel beta subunit: physiological consequences and pathophysiological effects in models of cardiac hypertrophy. Circ Res. 2007;101:166–175
  87. Ganesan AN, O’Rourke B, Maack C, Colecraft H, Sidor A, Johns DC. Reverse engineering the L-type Ca2+ channel alpha1c subunit in adult cardiac myocytes using novel adenoviral vectors. Biochem Biophys Res Commun. 2005;329:749–754

PII: S1443-9506(08)00949-9

doi: 10.1016/j.hlc.2008.11.004

Heart, Lung and Circulation
Volume 18, Issue 1 , Pages 3-10 , February 2009