Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy

Journal of Molecular Medicine

Volumn 84, Issue 5, 2006, Pages 349-364

  Oudit, Gavin Y ^a,b,c   Trivieri, Maria G ^a   Khaper, Neelam ^a   Liu, Peter P ^a   Backx, Peter H ^a,b,c,d  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b HEART AND STROKE FOUNDATION OF CANADA   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

^d Department of Physiology ^*  (Canada)

Author keywords

Cardiomyopathy; Endocrinopathy; Hemochromatosis; Iron; L type Ca 2+ channels; Oxidative stress

Indexed keywords

CALCIUM CHANNEL L TYPE; FERROUS ION; TRANSFERRIN;

ADENOHYPOPHYSIS DISEASE; CARDIOMYOPATHY; CONGESTIVE CARDIOMYOPATHY; DEGENERATIVE DISEASE; DIABETES MELLITUS; FRIEDREICH ATAXIA; GENE FREQUENCY; HEART ARRHYTHMIA; HEART DISEASE; HEART MUSCLE ISCHEMIA; HEMOCHROMATOSIS; HEMOSIDEROSIS; HUMAN; IRON OVERLOAD; IRON TRANSPORT; NERVE CELL; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; REPERFUSION INJURY; REVIEW;

BIOLOGICAL TRANSPORT; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, L-TYPE; CARDIOMYOPATHIES; CATION TRANSPORT PROTEINS; ENDOCRINE SYSTEM DISEASES; HEMOCHROMATOSIS; HUMANS; IRON; MYOCARDIUM; POISONING; RECEPTORS, TRANSFERRIN; TRANSFERRIN;

EID: 33646351076     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00109-005-0029-x     Document Type: Review

References (185)

1. Andrews NC (1999) Disorders of iron metabolism. N Engl J Med 341:1986-1995
2. Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts; molecular control of mammalian iron metabolism. Cell 117:285-297
3. Napier I, Ponka P, Richardson DR (2005) Iron trafficking in the mitochondrion: novel pathways revealed by disease. Blood 105:1867-1874
4. Weatherall DJ, Clegg JB (1996) Thalassemia - a global public health problem. Nat Med 2:847-849
5. Olivieri NF (1999) The beta-thalassemias. N Engl J Med 341:99-109
6. Weatherall DJ, Clegg JB (2001) Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ 79:704-712
7. Pietrangelo A (2004) Hereditary hemochromatosis - a new look at an old disease. N Engl J Med 350:2383-2397
8. Breuer W, Hershko C, Cabantchik ZI (2000) The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci 23:185-192
9. Templeton DM, Liu Y (2003) Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta 1619:113-124
10. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI (2003) Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 102:2670-3677
11. Kaplan J, Jordan I, Sturrock A (1991) Regulation of the transferrin-independent iron transport system in cultured cells. J Biol Chem 266:2997-3004
12. Randell EW, Parkes JG, Olivieri NF, Templeton DM (1994) Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. J Biol Chem 269:16046-16053
13. Liu P, Olivieri N (1994) Iron overload cardiomyopathies: new insights into an old disease. Cardiovasc Drugs Ther 8:101-110
14. Lee DH, Jacobs DR Jr (2004) Serum markers of stored body iron are not appropriate markers of health effects of iron: a focus on serum ferritin. Med Hypotheses 62:442-445
15. Gutteridge JM, Rowley DA, Griffiths E, Halliwell B (1985) Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci (Colch) 68:463-467
16. Artman M, Olson RD, Boucek RJ Jr, Boerth RC (1984) Depression of contractility in isolated rabbit myocardium following exposure to iron: role of free radicals. Toxicol Appl Pharmacol 72:324-332
17. Vernon DD, Banner W Jr, Dean JM (1989) Hemodynamic effects of experimental iron poisoning. Ann Emerg Med 18:863-866
18. Oudit GY, Sun H, Trivieri MG, Koch SE, Dawood F, Ackerley C, Yazdanpanah M, Wilson GJ, Schwartz A, Liu PP, Backx PH (2003) L-type Ca(2+) channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nat Med 9:1187-1194
19. Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, Sole MJ, Backx PH (2004) Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation 109:1877-1885
20. Seznec H, Simon D, Monassier L, Criqui-Filipe P, Gansmuller A, Rustin P, Koenig M, Puccio H (2004) Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia. Hum Mol Genet 13:1017-1024
21. Schafer AI, Cheron RG, Dluhy R, Cooper B, Gleason RE, Soeldner JS, Bunn HF (1981) Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 304:319-324
22. Italian Working Group (1995) Multicentre study on prevalence of endocrine complications in thalassaemia major. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Clin Endocrinol (Oxf) 42:581-586
23. Hempenius LM, Van Dam PS, Marx JJ, Koppeschaar HP (1999) Mineralocorticoid status and endocrine dysfunction in severe hemochromatosis. J Endocrinol Invest 22:369-376
24. Li CK, Luk CW, Ling SC, Chik KW, Yuen HL, Shing MM, Chang KO, Yuen PM (2002) Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study. Hong Kong Med J 8:255-260
25. Sinigaglia L, Fargion S, Fracanzani AL, Binelli L, Battafarano N, Varenna M, Piperno A, Fiorelli G (1997) Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol 24:1809-1813
26. Matsushima S, Torii M, Ozaki K, Narama I (2003) Iron lactate-induced osteomalacia in association with osteoblast dynamics. Toxicol Pathol 31:646-654
27. Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P, Choubtum L, Sriphrapradang A, Domrongkitchaiporn S, Sirisriro R, Rajatanavin R (2003) Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. J Clin Endocrinol Metab 88:3966-3972
28. Voest EE, Vreugdenhil G, Marx JJ (1994) Iron-chelating agents in non-iron overload conditions. Ann Intern Med 120:490-499
29. Turoczi T, Jun L, Cordis G, Morris JE, Maulik N, Stevens RG, Das DK (2003) HFE mutation and dietary iron content interact to increase ischemia/reperfusion injury of the heart in mice. Circ Res 92:1240-1246
30. de Valk B, Marx JJ (1999) Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 159:1542-1548
31. Ramakrishna G, Rooke TW, Cooper LT (2003) Iron and peripheral arterial disease: revisiting the iron hypothesis in a different light. Vasc Med 8:203-210
32. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, DiMonte D, Volitaskis I, Ellerby L, Cherny RA, Bush AI, Andersen JK (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 37:899-909
33. Todorich BM, Connor JR (2004) Redox metals in Alzheimer's disease. Ann N Y Acad Sci 1012:171-178
34. Rochette J, Pointon JJ, Fisher CA, Perera G, Arambepola M, Arichchi DS, De Silva S, Vandwalle JL, Monti JP, Old JM, Merryweather-Clarke AT, Weatherall DJ, Robson KJ (1999) Multicentric origin of hemochromatosis gene (HFE) mutations. Am J Hum Genet 64:1056-1062
35. Bulaj ZJ, Ajioka RS, Phillips JD, LaSalle BA, Jorde LB, Griffen LM, Edwards CQ, Kushner JP (2000) Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 343:1529-1535
36. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP (2004) Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36:77-82
37. Roetto A, Daraio F, Alberti F, Porporato P, Cali A, De Gobbi M, Camaschella C (2002) Hemochromatosis due to mutations in transferrin receptor 2. Blood Cells Mol Dis 29:465-470
38. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090-2093
39. De Domenico I, Ward DM, Nemeth E, Vaughn MB, Musci G, Ganz T, Kaplan J (2005) The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A 102:8955-8960
40. Gordeuk VR (2002) African iron overload. Semin Hematol 39:263-269
41. Loreal O, Gosriwatana I, Guyader D, Porter J, Brissot P, Hider RC (2000) Determination of non-transferrin-bound iron in genetic hemochromatosis using a new HPLC-based method. J Hepatol 32:727-733
42. Chen FE, Ooi C, Ha SY, Cheung BM, Todd D, Liang R, Chan TK, Chan V (2000) Genetic and clinical features of hemoglobin H disease in Chinese patients. N Engl J Med 343:544-550
43. Olivieri NF (2001) Progression of iron overload in sickle cell disease. Semin Hematol 38:57-62
44. Bottomley SS (2001) Iron overload in sideroblastic and other non-thalassemic anemias. In: Barton JC, Edwards CQ (eds) Hemochromatosis: genetics, pathophysiology, diagnosis, and treatment. Cambridge University Press, Cambridge, pp 442-467
45. Quinn CT, Rogers ZR, Buchanan GR (2004) Survival of children with sickle cell disease. Blood 103:4023-4027
46. Steinberg MH (1999) Management of sickle cell disease. N Engl J Med 340:1021-1030
47. Serjeant GR, Serjeant BE (2001) Sickle cell disease, 3rd edn. Oxford University Press, New York
48. Fleming MD (2002) The genetics of inherited sideroblastic anemias. Semin Hematol 39:270-281
49. Zager RA, Johnson AC, Hanson SY, Wasse H (2002) Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 40:90-103
50. Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH (2001) Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis 37:564-572
51. Kletzmayr J, Horl WH (2002) Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant 17 (Suppl 2):25-29
52. Engle JP, Polin KS, Stile IL (1987) Acute iron intoxication: treatment controversies. Drug Intell Clin Pharm 21:153-159
53. Tenenbein M, Kopelow ML, deSa DJ (1988) Myocardial failure and shock in iron poisoning. Human Toxicol 7:281-284
54. Fine JS (2000) Iron poisoning. Curr Probl Pediatr 30:71-90
55. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 21:195-199
56. Robb A, Wessling-Resnick M (2004) Regulation of transferrin receptor 2 protein levels by transferrin. Blood 104:4294-4299
57. Johnson MB, Enns CA (2004) Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104:4287-4293
58. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482-488
59. Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, Hentze MW, Rouault TA, Andrews NC, Hediger MA (2001) Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 509:309-316
60. Ke Y, Chen YY, Chang YZ, Duan XL, Ho KP, Jiang de H, Wang K, Qian ZM (2003) Post-transcriptional expression of DMT1 in the heart of rat. J Cell Physiol 196:124-130
61. Quigley JG, Yang Z, Worthington MT, Phillips JD, Sabo KM, Sabath DE, Berg CL, Sassa S, Wood BL, Abkowitz JL (2004) Identification of a human heme exporter that is essential for erythropoiesis. Cell 118:757-766
62. Thomas C, Oates PS (2004) Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut 53:44-49
63. Scheiber-Mojdehkar B, Lutzky B, Schaufler R, Sturm B, Goldenberg H (2004) Non-transferrin-bound iron in the serum of hemodialysis patients who receive ferric saccharate: no corretion to peroxide generation. J Am Soc Nephrol 15:1648-1655
64. Parkes JG, Olivieri NF, Templeton DM (1997) Characterization of Fe2+ and Fe3+ transport by iron-loaded cardiac myocytes. Toxicology 117:141-151
65. Lansman JB, Hess P, Tsien RW (1986) Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore. J Gen Physiol 88:321-347
66. Winegar BD, Kelly R, Lansman JB (1991) Block of current through single calcium channels by Fe, Co, and Ni. Location of the transition metal binding site in the pore. J Gen Physiol 97:351-367
67. Atar D, Backx PH, Appel MM, Gao WD, Marban E (1995) Excitation-transcription coupling mediated by zinc influx through voltage-dependent calcium channels. J Biol Chem 270:2473-2477
68. Tsushima RG, Wickenden AD, Bouchard RA, Oudit GY, Liu PP, Backx PH (1999) Modulation of iron uptake in heart by L-type Ca2+ channel modifiers: possible implications in iron overload. Circ Res 84:1302-1309
69. Townsend A, Drakesmith H (2002) Role of HFE in iron metabolism, hereditary haemochromatosis, anaemia of chronic disease, and secondary iron overload. Lancet 359:786-790
70. Laftah AH, Ramesh B, Simpson RJ, Solanky N, Bahram S, Schumann K, Debnam ES, Srai SK (2004) Effect of hepcidin on intestinal iron absorption in mice. Blood 103:3940-3944
71. Ludwiczek S, Theurl I, Bahram S, Schumann K, Weiss G (2005) Regulatory networks for the control of body iron homeostasis and their dysregulation in HFE mediated hemochromatosis. J Cell Physiol 204:489-499
72. Yamaji S, Sharp P, Ramesh B, Srai SK (2004) Inhibition of iron transport across human intestinal epithelial cells by hepcidin. Blood 104:2178-2180
73. Muckenthaler M, Roy CN, Custodio AO, Minana B, deGraaf J, Montross LK, Andrews NC, Hentze MW (2003) Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrdl expression in mouse hemochromatosis. Nat Genet 34:102-107
74. Celec P (2005) Hemojuvelin: a supposed role in iron metabolism one year after its discovery. J Mol Med 83:521-525
75. Niederkofler V, Salie R, Arber S (2005) Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 115:2180-2186
76. Ward RJ, Kuhn LC, Kaldy P, Florence A, Peters TJ, Crichton RR (1994) Control of cellular iron homeostasis by iron-responsive elements in vivo. Eur J Biochem 220:927-931
77. Pantopoulos K (2004) Iron metabolism and the IRE/IRP regulatory system: an update. Ann N Y Acad Sci 1012:1-13
78. Meyron-Holtz EG, Ghosh MC, Rouault TA (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:2087-2090
79. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR (1994) Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 331:574-578
80. Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW (1994) Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331:567-573
81. Zurlo MG, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, Di Gregorio F, Burattini MG, Terzoli S (1989) Survival and causes of death in thalassaemia major. Lancet 2:27-30
82. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110:1107-1119
83. Cecchetti G, Binda A, Piperno A, Nador F, Fargion S, Fiorelli G (1991) Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation. Eur Heart J 12:224-230
84. Muhlestein JB (2000) Cardiac abnormalities in hemochromatosis. In: Barton JC, Edwards CQ (eds) Hemochromatosis: genetics, pathophysiology, diagnosis, and treatment. Cambridge University Press, Cambridge, pp 297-310
85. Palka P, Macdonald G, Lange A, Burstow DJ (2002) The role of Doppler left ventricular filling indexes and Doppler tissue echocardiography in the assessment of cardiac involvement in hereditary hemochromatosis. J Am Soc Echocardiogr 15:884-890
86. Modell B, Khan M, Darlison M (2000) Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 355:2051-2052
87. Veglio F, Melchio R, Rabbia F, Molino P, Geneva GC, Martini G, Schiavone D, Piga A, Chiandussi L (1998) Blood pressure and heart rate in young thalassemia major patients. Am J Hypertens 11:539-547
88. Kremastinos DT, Tsiapras DP, Tsetsos GA, Rentoukas EI, Vretou HP, Toutouzas PK (1993) Left ventricular diastolic Doppler characteristics in beta-thalassemia major. Circulation 88:1127-1135
89. Buja LM, Roberts WC (1971) Iron in the heart. Etiology and clinical significance. Am J Med 51:209-221
90. Mattheyses M, Hespel JP, Brissot P, Daubert JC, Hita de Nercy Y, Lancien G, Le Treut A, Pony JC, Simon M, Ferrand B, Gouffault J, Bourel M (1978) The cardiomyopathy of idiopathic hemochromatosis. Arch Mal Coeur Vaiss 71:371-379
91. Rosenqvist M, Hultcrantz R (1989) Prevalence of a haemochromatosis among men with clinically significant bradyarrhythmias. Eur Heart J 10:473-478
92. Laurita KR, Chuck ET, Yang T, Dong WQ, Kuryshev YA, Brittenham GM, Rosenbaum DS, Brown AM (2003) Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. J Lab Clin Med 142:83-89
93. Eaton JW, Qian M (2002) Molecular bases of cellular iron toxicity. Free Radic Biol Med 32:833-840
94. Kadiiska MB, Burkitt MJ, Xiang QH, Mason RP (1995) Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation. J Clin Invest 96:1653-1657
95. Young IS, Trouton TG, Torney JJ, McMaster D, Callender ME, Trimble ER (1994) Antioxidant status and lipid peroxidation in hereditary haemochromatosis. Free Radic Biol Med 16:393-397
96. Livrea MA, Tesoriere L, Pintaudi AM, Calabrese A, Maggio A, Freisleben HJ, D'Arpa D, D'Anna R, Bongiorno A (1996) Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood 88:3608-3614
97. Lim PS, Chan EC, Lu TC, Yu YL, Kuo SY, Wang TH, Wei YH (2000) Lipophilic antioxidants and iron status in ESRD patients on hemodialysis. Nephron 86:428-435
98. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81-128
99. Lee SH, Oe T, Blair IA (2001) Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science 292:2083-2086
100. Valenti L, Conte D, Piperno A, Dongiovanni P, Fracanzani AL, Fraquelli M, Vergani A, Gianni C, Carmagnola L, Fargion S (2004) The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. J Med Genet 41:946-950
101. Kremastinos DT, Tiniakos G, Theodorakis GN, Katritsis DG, Toutouzas PK (1995) Myocarditis in beta-thalassemia major. A cause of heart failure. Circulation 91:66-71
102. Kremastinos DT, Flevari P, Spyropoulou M, Vrettou H, Tsiapras D, Stavropoulos-Giokas CG (1999) Association of heart failure in homozygous beta-thalassemia with the major histocompatibility complex. Circulation 100:2074-2078
103. Economou-Petersen E, Aessopos A, Kladi A, Flevari P, Karabatsos F, Fragodimitri C, Nicolaidis P, Vrettou H, Vassilopoulos D, Karagiorga-Lagana M, Kremastinos DT, Petersen MB (1998) Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia. Blood 92:3455-3459
104. Cooper JM, Schapira AH (2003) Friedreich's ataxia: disease mechanisms, antioxidant and coenzyme Q10 therapy. Biofactors 18:163-171
105. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662
106. Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521-555
107. Mukherjee R, Spinale FG (1998) L-type calcium channel abundance and function with cardiac hypertrophy and failure: a review. J Mol Cell Cardiol 30:1899-1916
108. Bers DM (2002) Excitation-contraction coupling and cardiac contractile force, 2nd edn. Kluwer, Dordrecht, pp 101-132
109. Cherednichenko G, Zima AV, Feng W, Schaefer S, Blatter LA, Pessah IN (2004) NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release. Circ Res 94:478-486
110. Goldhaber JI, Qayyum MS (2000) Oxygen free radicals and excitation-contraction coupling. Antioxid Redox Signal 2:55-64
111. Lacampagne A, Duittoz A, Bolanos P, Peineau N, Argibay JA (1995) Effect of sulfhydryl oxidation on ionic and gating currents associated with L-type calcium channels in isolated guinea-pig ventricular myocytes. Cardiovasc Res 30:799-806
112. Shirotani K, Katsura M, Higo A, Takesue M, Mohri Y, Shuto K, Tarumi C, Ohkuma S (2001) Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons. Brain Res Mol Brain Res 92:12-18
113. Kuryshev YA, Brittenham GM, Fujioka H, Kannan P, Shieh CC, Cohen SA, Brown AM (1999) Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease. Circulation 100:675-683
114. Horackova M, Ponka P, Byczko Z (2000) The antioxidant effects of a novel iron chelator salicylaldehyde isonicotinoyl hydrazone in the prevention of H(2)O(2) injury in adult cardiomyocytes. Cardiovasc Res 47:529-536
115. Folden DV, Gupta A, Sharma AC, Li SY, Saari JT, Ren J (2003) Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism. Br J Pharmacol 139:1310-1316
116. Schwartz KA, Li Z, Schwartz DE, Cooper TG, Braselton WE (2002) Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction. J Appl Physiol 93:746-751
117. Tomaselli GF, Zipes DP (2004) What causes sudden death in heart failure? Cire Res 95:754-763
118. Barrington PL, Martin RL, Zhang K (1997) Slowly inactivating sodium currents are reduced by exposure to oxidative stress. J Mol Cell Cardiol 29:3251-3265
119. Wu VC, Huang JW, Wu MS, Chin CY, Chiang FT, Liu YB, Wu KD (2004) The effect of iron stores on corrected QT dispersion in patients undergoing peritoneal dialysis. Am J Kidney Dis 44:720-728
120. Gaenzer H, Marschang P, Sturm W, Neumayr G, Vogel W, Patsch J, Weiss G (2002) Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol 40:2189-2194
121. Cheung YF, Chan GC, Ha SY (2002) Arterial stiffness and endothelial function in patients with beta-thalassemia major. Circulation 106:2561-2566
122. Lemogoum D, Van Bortel L, Najem B, Dzudie A, Teutcha C, Madu E, Leeman M, Degaute JP, van de Borne P (2004) Arterial stiffness and wave reflections in patients with sickle cell disease. Hypertension 44:924-929
123. Liu Y, Parkes JG, Templeton DM (2003) Differential accumulation of non-transferrin-bound iron by cardiac myocytes and fibroblasts. J Mol Cell Cardiol 35:505-514
124. Hess P, Lansman JB, Tsien RW (1986) Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol 88:293-319
125. Rychkov G, Brereton HM, Harland ML, Barritt GJ (2001) Plasma membrane Ca2+ release-activated Ca2+ channels with a high selectivity for Ca2+ identified by patch-clamp recording in rat liver cells. Hepatology 33:938-947
126. Jorgensen NR, Teilmann SC, Henriksen Z, Civitelli R, Sorensen OH, Steinberg TH (2003) Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells. J Biol Chem 278:4082-4086
127. Rorsman P, Renstrom E (2003) Insulin granule dynamics in pancreatic beta cells. Diabetologia 46:1029-1045
128. Sinnegger-Brauns MJ, Hetzenauer A, Huber IG, Renstrom E, Wietzorrek G, Berjukov S, Cavalli M, Walter D, Koschak A, Waldschutz R, Hering S, Bova S, Rorsman P, Pongs O, Singewald N, Striessnig JJ (2004) Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest 113:1430-1439
129. Van Goor F, Zivadinovic D, Stojilkovic SS (2001) Differential expression of ionic channels in rat anterior pituitary cells. Mol Endocrinol 15:1222-1236
130. Tsien RW, Hess P, McCleskey EW, Rosenberg RL (1987) Calcium channels: mechanisms of selectivity, permeation, and block. Annu Rev Biophys Biophys Chem 16:265-290
131. Cataldi M, Perez-Reyes E, Tsien RW (2002) Differences in apparent pore sizes of low and high voltage-activated Ca2+ channels. J Biol Chem 277:45969-45976
132. Abernethy DR, Schwartz JB (1999) Calcium-antagonist drugs. N Engl J Med 341:1447-1457
133. Lipscombe D (2002) L-type calcium channels: highs and new lows. Circ Res 90:933-935
134. Han W, Chartier D, Li D, Nattel S (2001) Ionic remodeling of cardiac Purkinje cells by congestive heart failure. Circulation 104:2095-2100
135. Biel M, Schneider A, Wahl C (2002) Cardiac HCN channels: structure, function, and modulation. Trends Cardiovasc Med 12:206-212
136. Mitcheson JS, Hancox JC (1997) Modulation by mexiletine of action potentials, L-type Ca current and delayed rectifier K current recorded from isolated rabbit atrioventricular nodal myocytes. Pflugers Arch 434:855-858
137. Verkerk AO, Wilders R, Coronel R, Ravesloot JH, Verheijck EE (2003) Ionic remodeling of sinoatrial node cells by heart failure. Circulation 108:760-766
138. Fassos FF, Berkovitch M, Daneman N, Koren L, Cameron R, Klein J, Falcitelli C, St Louis P, Daneman R, Koren G (1998) The efficacy of diazepam in the treatment of acute iron overload in rats. Can J Physiol Pharmacol 76:895-899
139. Hara Y, Kobayashi H, Ooshiro S, Futamura K, Nishino T, Chugun A, Temma K, Kondo H (2001) Negative inotropic effect of diazepam in isolated guinea pig heart. J Vet Med Sci 63:135-143
140. Knabb RM, Rosamond TL, Fox KA, Sobel BE, Bergmann SR (1986) Enhancement of salvage of reperfused ischemic myocardium by diltiazem. J Am Coll Cardiol 8:861-871
141. Ehring T, Heusch G (1995) Stunned myocardium and the attenuation of stunning by calcium antagonists. Am J Cardiol 75:61E-67E
142. Horwitz LD, Rosenthal EA (1999) Iron-mediated cardiovascular injury. Vasc Med 4:93-99
143. Murray MT, White K, Munro HN (1987) Conservation of ferritin heavy subunit gene structure: implications for the regulation of ferritin gene expression. Proc Natl Acad Sci U S A 84:7438-7442
144. Sah R, Oudit GY, Nguyen TT, Lim HW, Wickenden AD, Wilson GJ, Molkentin JD, Backx PH (2002) Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice. Circulation 105:1850-1856
145. O'Neill HA, Galch O, Park S, Cui J, Mooney SM, Sampson M, Ferreira GC, Isaya G (2005) Assembly of human frataxin is a mechanism for detoxifying redox-active iron. Biochemistry 44:537-545
146. Sturm B, Bistrich U, Schranzhofer M, Sarsero JP, Rauen U, Scheiber-Mojdehkar B, de Groot H, Ioannou P, Petrat F (2005) Friedreich's ataxia, no changes in mitochondrial labile iron in human lymphoblasts and fibroblasts: a decrease in antioxidative capacity? J Biol Chem 280:6701-6708
147. Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276:1709-1712
148. Liu L, O'Hara DS, Cala SE, Poornima I, Hines RN, Marsh JD (2000) Developmental regulation of the L-type calcium channel alphalC subunit expression in heart. Mol Cell Biochem 205:101-109
149. Hezareh M, Schlegel W, Rawlings SR (1997) Stimulation of Ca2+ influx in alpha T3-1 gonadotrophs via the cAMP/PKA signaling system. Am J Physiol 273:E850-E858
150. Anderson L, Hoyland J, Mason WT, Eidne KA (1992) Characterization of the gonadotrophin-releasing hormone calcium response in single alpha T3-1 pituitary gonadotroph cells. Mol Cell Endocrinol 86:167-175
151. Mulvaney JM, Zhang T, Fewtrell C, Roberson MS (1999) Calcium influx through L-type channels is required for selective activation of extracellular signal-regulated kinase by gonadotropin-releasing hormone. J Biol Chem 274:29796-29804
152. Shupnik MA, Weck J, Hinkle PM (1996) Thyrotropin (TSH)-releasing hormone stimulates TSH beta promoter activity by two distinct mechanisms involving calcium influx through L type Ca2+ channels and protein kinase C. Mol Endocrinol 10:90-99
153. Fiekers JF, Konopka LM (1996) Spontaneous transients of [Ca2+]i depend on external calcium and the activation of L-type voltage-gated calcium channels in a clonal pituitary cell line (AtT-20) of cultured mouse corticotropes. Cell Calcium 19:327-336
154. Chang W, Pratt SA, Chen TH, Tu CL, Mikala G, Schwartz A, Shoback D (2001) Parathyroid cells express dihydropyridine-sensitive cation currents and L-type calcium channel subunits. Am J Physiol Endocrinol Metab 281:E180-E189
155. Rahier J, Loozen S, Goebbels RM, Abrahem M (1987) The haemochromatotic human pancreas: a quantitative immunohistochemical and ultrastructural study. Diabetologia 30:5-12
156. Argyropoulou MI, Kiortsis DN, Metafratzi Z, Bitsis S, Tsatoulis A, Efremidis SC (2001) Pituitary gland height evaluated by MR in patients with beta-thalassemia major: a marker of pituitary gland function. Neuroradiology 43:1056-1058
157. Economou M, Katzos G, Koussi A, Tsatra I, Athanassiou-Metaxa M (2003) Hypoparathyroidism in beta-thalassemic patients. J Pediatr Hematol Oncol 25:275-276 (author reply 276)
158. Cario H, Holl RW, Debatin KM, Kohne E (2003) Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test. Eur J Pediatr 162:139-146
159. Flynn JT, Pasko DA (2000) Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension. Pediatr Nephrol 15:302-316
160. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia-Barreto D, Keltai M, Erdine S, Bristol HA, Kolb HR, Bakris GL, Cohen JD, Parmley WW (2003) A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 290:2805-2816
161. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A (2004) Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 363:2022-2031
162. Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198-205
163. Mikus G, Eichelbaum M, Fischer C, Gumulka S, Klotz U, Kroemer HK (1990) Interaction of verapamil and cimetidine: stereochemical aspects of drug metabolism, drug disposition and drug action. J Pharmacol Exp Ther 253:1042-1048
164. Fuhr U, Muller-Peltzer H, Kern R, Lopez-Rojas P, Junemann M, Harder S, Staib AH (2002) Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 58:45-53
165. Elliott HL, Elawad M, Wilkinson R, Singh SP (2002) Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system. J Hypertens 20:333-338
166. Murphy SW (2004) Diastolic dysfunction. Curr Treat Options Cardiovasc Med 6:61-68
167. Mason RP, Marche P, Hintze TH (2003) Novel vascular biology of third-generation L-type calcium channel antagonists: ancillary actions of amlodipine. Arterioscler Thromb Vasc Biol 23:2155-2163
168. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Jr., Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK, et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399-408
169. Levy JE, Montross LK, Cohen DE, Fleming MD, Andrews NC (1999) The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94:9-11
170. Roetto A, Daraio F, Porporato P, Caruso R, Cox TM, Cazzola M, Gasparini P, Piperno A, Camaschella C (2003) Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70r). Blood
171. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P (2000) The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25:14-15
172. Fleming RE, Ahmann JR, Migas MC, Waheed A, Koeffler HP, Kawabata H, Britton RS, Bacon BR, Sly WS (2002) Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A 99:10653-10658
173. Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P (2001) A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet 28:213-214
174. Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A (2001) Autosomaldominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 108:619-623
175. Shehee WR, Oliver P, Smithies O (1993) Lethal thalassemia after insertional disruption of the mouse major adult beta-globin gene. Proc Natl Acad Sci U S A 90:3177-3181
176. Yang B, Kirby S, Lewis J, Detloff P, Maeda N, Smithies O (1995) A Mouse Model for {beta]0-Thalassemia. PNAS 92:11608-11612
177. Paszty C, Brion CM, Manci E, Witkowska HE, Stevens ME, Mohandas N, Rubin EM (1997) Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science 278:876-878
178. Ryan TM, Ciavatta DJ, Townes TM (1997) Knockout-transgenic mouse model of sickle cell disease. Science 278:873-876
179. Yamamoto M, Nakajima O (2000) Animal models for X-linked sideroblastic anemia. Int J Hematol 72:157-164
180. Nakajima O, Takahashi S, Harigae H, Furuyama K, Hayashi N, Sassa S, Yamamoto M (1999) Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J 18:6282-6289
181. Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, Griesshammer A, Marquardt T, Janka-Schaub G, Kron M, Kohne E (2003) Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation. Blood 102:4576-4581
182. Lim PS, Wei YH, Yu YL, Kho B (1999) Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 14:2680-2687
183. Safa P, Boulter J, Hales TG (2001) Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells. J Biol Chem 276:38727-38737
184. LeBeau AP, Robson AB, McKinnon AE, Donald RA, Sneyd J (1997) Generation of action potentials in a mathematical model of corticotrophs. Biophys J 73:1263-1275
185. Misler S, Barnett DW, Gillis KD, Pressel DM (1992) Electrophysiology of stimulus-secretion coupling in human beta-cells. Diabetes 41:1221-1228