(Journal Article): The L-type calcium channel in the heart: the beat goes on
 
Bodi I, Mikala G, Koch SE, Akhter SA, Schwartz A (Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Department of Surgery, Cincinnati, Ohio, USA, schwara@email.uc.edu )
 
IN: J Clin Invest 2005; 115(12):3306-3317
Impact Factor(s) of J Clin Invest: 14.204 (2004), 14.307 (2003), 14.118 (2001)

Fulltext:    HTML  PDF

ABSTRACT: Sydney Ringer would be overwhelmed today by the implications of his simple experiment performed over 120 years ago showing that the heart would not beat in the absence of Ca2+. Fascination with the role of Ca2+ has proliferated into all aspects of our

TYPE OF PUBLICATION: Review

REFERENCES:

1. Ringer S. A further contribution regarding the influence of the different constituents of the blood on the contraction of the heart. J Physiol 1883. 4:29-47. [DOD]
2. Carafoli E, Santella L, Branca D, Brini M. Generation, control, and processing of cellular calcium signals. Crit Rev Biochem Mol Biol 2001. 36:107-260. [DOD]
3. Ellis SB, Williams ME, Ways NR, Brenner R, Sharp AH, Leung AT, Campbell KP, McKenna E, Koch WJ, Hui A. Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel. Science 1988. 241:1661-1664. [DOD]
4. Mori Y. Molecular pharmacology of voltage-dependent calcium channels. Jpn J Pharmacol 1996. 72:83-109. [DOD]
5. Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 2000. 16:521-555. [DOD]
6. Finkbeiner S, Greenberg ME. Ca2+ channel-regulated neuronal gene expression. J Neurobiol 1998. 37:171-189. [DOD]
7. Rottbauer W, Baker K, Wo ZG, Mohideen MA, Cantiello HF, Fishman MC. Growth and function of the embryonic heart depend upon the cardiac-specific L-type calcium channel alpha1 subunit. Dev Cell 2001. 1:265-275. [DOD]
8. Qin N, Platano D, Olcese R, Stefani E, Birnbaumer L. Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors. Proc Natl Acad Sci U S A 1997. 94(16):8866-8871. [DOD]
9. Yokoyama CT, Myers SJ, Fu J, Mockus SM, Scheuer T, Catterall WA. Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site. Mol Cell Neurosci 2005. 28(1):1-17. [DOD]
10. Perez-Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 2003. 83:117-161. [DOD]
11. Lee JH, Cribbs LL, Perez-Reyes E. Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels. FEBS Lett 1999. 445:231-236. [DOD]
12. Takahashi M, Catterall WA. Dihydropyridine-sensitive calcium channels in cardiac and skeletal muscle membranes: studies with antibodies against the alpha subunits. Biochemistry 1987. 26(17):5518-5526. [DOD]
13. Cataldi M, Perez-Reyes E, Tsien RW. Differences in apparent pore sizes of low and high voltage-activated Ca2+ channels. J Biol Chem 2002. 277(48):45969-45976. [DOD]
14. Klockner U, Mikala G, Schwartz A, Varadi G. Molecular studies of the asymmetric pore structure of the human cardiac voltage-dependent Ca2+ channel. Conserved residue, Glu-1086, regulates proton-dependent ion permeation. J Biol Chem 1996. 271(37):22293-22296. [DOD]
15. Mikala G, Bahinski A, Yatani A, Tang S, Schwartz A. Differential contribution by conserved glutamate residues to an ion-selectivity site in the L-type Ca2+ channel pore. FEBS Lett 1993. 335(2):265-269. [DOD]
16. Koch SE, Bodi I, Schwartz A, Varadi G. Architecture of Ca(2+) channel pore-lining segments revealed by covalent modification of substituted cysteines. J Biol Chem 2000. 275(44):34493-34500. [DOD]
17. Bezanilla F. Voltage sensor movements. J Gen Physiol 2002. 120(4):465-473. [DOD]
18. Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R. The principle of gating charge movement in a voltage-dependent K+ channel. Nature 2003. 423(6935):42-48. [DOD]
19. Starace DM, Bezanilla F. A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 2004. 427(6974):548-553. [DOD]
20. De Jongh KS, Warner C, Catterall WA. Subunits of purified calcium channels. Alpha 2 and delta are encoded by the same gene. J Biol Chem 1990. 265(25):14738-14741. [DOD]
21. Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR. Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Mol Pharmacol 2002. 62(3):485-496. [DOD]
22. Muth JN, Varadi G, Schwartz A. Use of transgenic mice to study voltage-dependent Ca2+ channels. Trends Pharmacol Sci 2001. 22(10):526-532. [DOD]
23. Hofmann F, Biel M, Flockerzi V. Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci 1994. 17:399-418. [DOD]
24. Varadi G, Lory P, Schultz D, Varadi M, Schwartz A. Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel. Nature 1991. 352(6331):159-162. [DOD]
25. Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol 2002. 135(1):257-265. [DOD]
26. Marais E, Klugbauer N, Hofmann F. Calcium channel alpha(2)delta subunits-structure and Gabapentin binding. Mol Pharmacol 2001. 59(5):1243-1248. [DOD]
27. Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, Myers RR. Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 2002. 303(3):1199-1205. [DOD]
28. Ivanov SV, Ward JM, Tessarollo L, McAreavey D, Sachdev V, Fananapazir L, Banks MK, Morris N, Djurickovic D, Devor-Henneman DE, Wei MH, Alvord GW, Gao B, Richardson JA, Minna JD, Rogawski MA, Lerman MI. Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene. Am J Pathol 2004. 165(3):1007-1018. [DOD]
29. Abernethy DR, Soldatov NM. Structure-functional diversity of human L-type Ca2+ channel: perspectives for new pharmacological targets. J Pharmacol Exp Ther 2002. 300(3):724-728. [DOD]
30. Arikkath J, Campbell KP. Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr Opin Neurobiol 2003. 13(3):298-307. [DOD]
31. Kang MG, Campbell KP. Gamma subunit of voltage-activated calcium channels. J Biol Chem 2003. 278(24):21315-21318. [DOD]
32. De Waard M, Pragnell M, Campbell KP. Ca2+ channel regulation by a conserved beta subunit domain. Neuron 1994. 13(2):495-503.
33. Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch TP, Campbell KP. Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature 1994. 368(6466):67-70.
34. Opatowsky Y, Chomsky-Hecht O, Kang MG, Campbell KP, Hirsch JA. The voltage-dependent calcium channel beta subunit contains two stable interacting domains. J Biol Chem 2003. 278(52):52323-52332.
35. Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr. Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature 2004. 429(6992):671-675.
36. Chen YH, Li MH, Zhang Y, He LL, Yamada Y, Fitzmaurice A, Shen Y, Zhang H, Tong L, Yang J. Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature 2004. 429(6992):675-680.
37. Bichet D, Cornet V, Geib S, Carlier E, Volsen S, Hoshi T, Mori Y, De Waard M. The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 2000. 25(1):177-190.
38. Hanlon MR, Berrow NS, Dolphin AC, Wallace BA. Modelling of a voltage-dependent Ca2+ channel beta subunit as a basis for understanding its functional properties. FEBS Lett 1999. 445:366-370.
39. McGee AW, Nunziato DA, Maltez JM, Prehoda KE, Pitt GS, Bredt DS. Calcium channel function regulated by the SH3-GK module in beta subunits. Neuron 2004. 42(1):89-99.
40. Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N. The roles of the subunits in the function of the calcium channel. Science 1991. 253(5027):1553-1557.
41. Muth JN, Bodi I, Lewis W, Varadi G, Schwartz A. A Ca(2+)-dependent transgenic model of cardiac hypertrophy: A role for protein kinase Calpha. Circulation 2001. 103(1):140-147.
42. Chien AJ, Zhao X, Shirokov RE, Puri TS, Chang CF, Sun D, Rios E, Hosey MM. Roles of a membrane-localized beta subunit in the formation and targeting of functional L-type Ca2+ channels. J Biol Chem 1995. 270(50):30036-30044.
43. Mikala G, Klockner U, Varadi M, Eisfeld J, Schwartz A, Varadi G. cAMP-dependent phosphorylation sites and macroscopic activity of recombinant cardiac L-type calcium channels. Mol Cell Biochem 1998. 185:95-109.
44. Schuhmann K, Voelker C, Hofer GF, Pflugelmeier H, Klugbauer N, Hofmann F, Romanin C, Groschner K. Essential role of the beta subunit in modulation of C-class L-type Ca2+ channels by intracellular pH. FEBS Lett 1997. 408(1):75-80.
45. Cens T, Mangoni ME, Richard S, Nargeot J, Charnet P. Coexpression of the beta2 subunit does not induce voltage-dependent facilitation of the class C L-type Ca channel. Pflugers Arch 1996. 431(5):771-774.
46. Tareilus E, Roux M, Qin N, Olcese R, Zhou J, Stefani E, Birnbaumer L. A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit. Proc Natl Acad Sci U S A 1997. 94(5):1703-1708.
47. Yamaguchi H, Hara M, Strobeck M, Fukasawa K, Schwartz A, Varadi G. Multiple modulation pathways of calcium channel activity by a beta subunit. Direct evidence of beta subunit participation in membrane trafficking of the alpha1C subunit. J Biol Chem 1998. 273(30):19348-19356.
48. Kobrinsky E, Tiwari S, Maltsev VA, Harry JB, Lakatta E, Abernethy DR, Soldatov NM. 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(13):12474-12485.
49. Viard P, Butcher AJ, Halet G, Davies A, Nurnberg B, Heblich F, Dolphin AC. PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane. Nat Neurosci 2004. 7(9):939-946.
50. Gregg RG, Messing A, Strube C, Beurg M, Moss R, Behan M, Sukhareva M, Haynes S, Powell JA, Coronado R, Powers PA. Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling. Proc Natl Acad Sci U S A 1996. 93(24):13961-13966.
51. Ball SL, Powers PA, Shin HS, Morgans CW, Peachey NS, Gregg RG. Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest Ophthalmol Vis Sci 2002. 43(5):1595-1603.
52. Murakami M, Yamamura H, Murakami A, Okamura T, Nunoki K, Mitui-Saito M, Muraki K, Hano T, Imaizumi Y, Flockerzi T, Yanagisawa T. Conserved smooth muscle contractility and blood pressure increase in response to high-salt diet in mice lacking the beta3 subunit of the voltage-dependent calcium channel. J Cardiovasc Pharmacol 2000. 36(Suppl 2):S69-S73.
53. Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V. Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J 1992. 11(3):885-890.
54. Chien AJ, Carr KM, Shirokov RE, Rios E, Hosey MM. Identification of palmitoylation sites within the L-type calcium channel beta2a subunit and effects on channel function. J Biol Chem 1996. 271(43):26465-26468.
55. Qin N, Platano D, Olcese R, Costantin JL, Stefani E, Birnbaumer L. Unique regulatory properties of the type 2a Ca2+ channel beta subunit caused by palmitoylation. Proc Natl Acad Sci U S A 1998. 95(8):4690-4695.
56. Colecraft HM, Alseikhan B, Takahashi SX, Chaudhuri D, Mittman S, Yegnasubramanian V, Alvania RS, Johns DC, Marban E, Yue DT. Novel functional properties of Ca(2+) channel beta subunits revealed by their expression in adult rat heart cells. J Physiol 2002. 541:435-452.
57. Murakami M, Fleischmann B, De Felipe C, Freichel M, Trost C, Ludwig A, Wissenbach U, Schwegler H, Hofmann F, Hescheler J, Flockerzi V, Cavalie A. Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels. J Biol Chem 2002. 277(43):40342-40351.
58. Murakami M, Yamamura H, Suzuki T, Kang MG, Ohya S, Murakami A, Miyoshi I, Sasano H, Muraki K, Hano T, Kasai N, Nakayama S, Campbell KP, Flockerzi V, Imaizumi Y, Yanagisawa T, Iijima T. Modified cardiovascular L-type channels in mice lacking the voltage-dependent Ca2+ channel beta3 subunit. J Biol Chem 2003. 278(44):43261-43267.
59. Hullin R, Khan IF, Wirtz S, Mohacsi P, Varadi G, Schwartz A, Herzig S. Cardiac L-type calcium channel beta-subunits expressed in human heart have differential effects on single channel characteristics. J Biol Chem 2003. 278(24):21623-21630.
60. Wei SK, Colecraft HM, DeMaria CD, Peterson BZ, Zhang R, Kohout TA, Rogers TB, Yue DT. Ca(2+) channel modulation by recombinant auxiliary beta subunits expressed in young adult heart cells. Circ Res 2000. 86(2):175-184.
61. Groner F, Rubio M, Schulte-Euler P, Matthes J, Khan IF, Bodi I, Koch SE, Schwartz A, Herzig S. Single-channel gating and regulation of human L-type calcium channels in cardiomyocytes of transgenic mice. Biochem Biophys Res Commun 2004. 314(3):878-884.
62. Song LS, Guia A, Muth JN, Rubio M, Wang SQ, Xiao RP, Josephson IR, Lakatta EG, Schwartz A, Cheng H. Ca(2+) signaling in cardiac myocytes overexpressing the alpha(1) subunit of L-type Ca(2+) channel. Circ Res 2002. 90(2):174-181.
63. Zuhlke RD, Pitt GS, Tsien RW, Reuter H. Ca2+-sensitive inactivation and facilitation of L-type Ca2+ channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the(alpha)1C subunit. J Biol Chem 2000. 275(28):21121-21129.
64. Zuhlke RD, Pitt GS, Deisseroth K, Tsien RW, Reuter H. Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature 1999. 399(6732):159-162.
65. Peterson BZ, DeMaria CD, Adelman JP, Yue DT. Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels. Neuron 1999. 22(3):549-558.
66. Peterson BZ, Lee JS, Mulle JG, Wang Y, de Leon M, Yue DT. Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels. Biophys J 2000. 78(4):1906-1920.
67. Pitt GS, Zuhlke RD, Hudmon A, Schulman H, Reuter H, Tsien RW. Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels. J Biol Chem 2001. 276(33):30794-30802.
68. Kim J, Ghosh S, Nunziato DA, Pitt GS. Identification of the components controlling inactivation of voltage-gated Ca2+ channels. Neuron 2004. 41(5):745-754.
69. Yang D, Song LS, Zhu WZ, Chakir K, Wang W, Wu C, Wang Y, Xiao RP, Chen SR, Cheng H. Calmodulin regulation of excitation-contraction coupling in cardiac myocytes. Circ Res 2003. 92(6):659-667.
70. 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(3):173-177.
71. Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G, Price EE Jr, Thiel W, Guatimosim S, Song LS, Madu EC, Shah AN, Vishnivetskaya TA, Atkinson JB, Gurevich VV, Salama G, Lederer WJ, Colbran RJ, Anderson ME. Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 2005. 11(4):409-417.
72. Anderson ME. Calmodulin kinase and L-type calcium channels, a recipe for arrhythmias?. Trends Cardiovasc Med 2004. 14(4):152-161.
73. Tessier S, Karczewski P, Krause EG, Pansard Y, Acar C, Lang-Lazdunski M, Mercadier JJ, Hatem SN. Regulation of the transient outward K(+) current by Ca(2+)/calmodulin-dependent protein kinases II in human atrial myocytes. Circ Res 1999. 85(9):810-819.
74. Anderson ME. Calmodulin kinase signaling in heart: an intriguing candidate target for therapy of myocardial dysfunction and arrhythmias. Pharmacol Ther 2005. 106(1):39-55.
75. Muller FU, Neumann J, Schmitz W. Transcriptional regulation by cAMP in the heart. Mol Cell Biochem 2000. 212:11-17.
76. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991. 324(12):781-788.
77. Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, Miller AB, Neuberg GW, Frid D, Wertheimer JH, Cropp AB, DeMets DL. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 1996. 335(15):1107-1114.
78. Boden WE, Ziesche S, Carson PE, Conrad CH, Syat D, Cohn JN. Rationale and design of the Third Vasodilator-Heart Failure Trial (V-HeFT III): felodipine as adjunctive therapy to enalapril and loop diuretics with or without digoxin in chronic congestive heart failure. V-HeFT III investigators. Am J Cardiol 1996. 77(12):1078-1082.
79. Dunselman PH, Kuntze CE, van Bruggen A, Hamer JP, Scaf AH, Wessling H, Lie KI. Efficacy of felodipine in congestive heart failure. Eur Heart J 1989. 10(4):354-364.
80. Elkayam U, Amin J, Mehra A, Vasquez J, Weber L, Rahimtoola SH. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 1990. 82(6):1954-1961.
81. Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995. 92(5):1326-1331.
82. Anonymous. Improved diastolic function with the calcium antagonist nisoldipine (coat-core) in patients post myocardial infarction: results of the DEFIANT study. Doppler Flow and Echocardiography in Functional cardiac Insufficiency: Assessment of Nisoldipine Therapy. Eur Heart J 1992. 13(11):1496-1505.
83. Anonymous. Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II–DAVIT II). Am J Cardiol 1990. 66(10):779-785.
84. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, Neaton JD, Grimm RH Jr, Hansson L, Lacourciere Y, Muller J, Sleight P, Weber MA, Williams G, Wittes J, Zanchetti A, Anders RJ, CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 2003. 289(16):2073-2082.
85. The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group.. N Engl J Med 1988. 319(7):385-392.
86. Kostis JB, Lacy CR, Cosgrove NM, Wilson AC. Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction. Am Heart J 1997. 133(5):550-557.
87. Ibrahim OA, Dunlap ME. Combination pharmacologic therapies for heart failure: what next after angiotensin-converting enzyme inhibitors and beta-blockers?. Curr Heart Fail Rep 2005. 2(2):89-93.
88. He M, Bodi I, Mikala G, Schwartz A. Motif III S5 of L-type calcium channels is involved in the dihydropyridine binding site. A combined radioligand binding and electrophysiological study. J Biol Chem 1997. 272(5):2629-2633.
89. Hockerman GH, Johnson BD, Abbott MR, Scheuer T, Catterall WA. Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels in transmembrane segment IIIS6 and the pore region of the alpha1 subunit. J Biol Chem 1997. 272(30):18759-18765.
90. Hering S, Aczel S, Grabner M, Doring F, Berjukow S, Mitterdorfer J, Sinnegger MJ, Striessnig J, Degtiar VE, Wang Z, Glossmann H. Transfer of high sensitivity for benzothiazepines from L-type to class A (BI) calcium channels. J Biol Chem 1996. 271(40):24471-24475.
91. Schuster A, Lacinova L, Klugbauer N, Ito H, Birnbaumer L, Hofmann F. The IVS6 segment of the L-type calcium channel is critical for the action of dihydropyridines and phenylalkylamines. EMBO J 1996. 15(1):2365-2370.
92. Hockerman GH, Johnson BD, Scheuer T, Catterall WA. Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels. J Biol Chem 1995. 270(38):22119-22122.
93. Starmer CF, Grant AO, Strauss HC. Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 1984. 46(1):15-27.
94. Hering S, Berjukow S, Aczel S, Timin EN. Ca2+ channel block and inactivation: common molecular determinants. Trends Pharmacol Sci 1998. 19(11):439-443.
95. Hering S, Aczel S, Kraus RL, Berjukow S, Striessnig J, Timin EN. Molecular mechanism of use-dependent calcium channel block by phenylalkylamines: role of inactivation. Proc Natl Acad Sci U S A 1997. 94(24):13323-13328.
96. Motoike HK, Bodi I, Nakayama H, Schwartz A, Varadi G. A region in IVS5 of the human cardiac L-type calcium channel is required for the use-dependent block by phenylalkylamines and benzothiazepines. J Biol Chem 1999. 274(14):9409-9420.
97. Benitah JP, Gomez AM, Fauconnier J, Kerfant BG, Perrier E, Vassort G, Richard S. Voltage-gated Ca2+ currents in the human pathophysiologic heart: a review. Basic Res Cardiol 2002. 97(Suppl 1):I11-I18.
98. Haase H, Kresse A, Hohaus A, Schulte HD, Maier M, Osterziel KJ, Lange PE, Morano I. Expression of calcium channel subunits in the normal and diseased human myocardium. J Mol Med 1996. 74(2):99-104.
99. Hullin R, Asmus F, Ludwig A, Hersel J, Boekstegers P. Subunit expression of the cardiac L-type calcium channel is differentially regulated in diastolic heart failure of the cardiac allograft. Circulation 1999. 100(2):155-163.
100. Schroder F, Handrock R, Beuckelmann DJ, Hirt S, Hullin R, Priebe L, Schwinger RH, Weil J, Herzig S. Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. Circulation 1998. 98(10):969-976.
101. Bosch RF, Scherer CR, Rub N, Wohrl S, Steinmeyer K, Haase H, Busch AE, Seipel L, Kuhlkamp V. Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I(Ca,L) and I(to) in rapid atrial pacing in rabbits. J Am Coll Cardiol 2003. 41(5):858-869.
102. Schotten U, Haase H, Frechen D, Greiser M, Stellbrink C, Vazquez-Jimenez JF, Morano I, Allessie MA, Hanrath P. The L-type Ca2+-channel subunits alpha1C and beta2 are not downregulated in atrial myocardium of patients with chronic atrial fibrillation. J Mol Cell Cardiol 2003. 35(5):437-443.
103. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V. Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 1999. 44(1):121-131.
104. Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM. Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 1999. 85(5):428-436.
105. Christ T, Boknik P, Wohrl S, Wettwer E, Graf EM, Bosch RF, Knaut M, Schmitz W, Ravens U, Dobrev D. L-type Ca2+ current downregulation in chronic human atrial fibrillation is associated with increased activity of protein phosphatases. Circulation 2004. 110(17):2651-2657.
106. Brundel BJ, Van Gelder IC, Henning RH, Tieleman RG, Tuinenburg AE, Wietses M, Grandjean JG, Van Gilst WH, Crijns HJ. Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation 2001. 103(5):684-690.
107. Klein G, Schroder F, Vogler D, Schaefer A, Haverich A, Schieffer B, Korte T, Drexler H. Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. Role of phosphatase 2A. Cardiovasc Res 2003. 59(1):37-45.
108. He J, Conklin MW, Foell JD, Wolff MR, Haworth RA, Coronado R, Kamp TJ. Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure. Cardiovasc Res 2001. 49(2):298-307.
109. Boixel C, Gonzalez W, Louedec L, Hatem SN. Mechanisms of L-type Ca(2+) current downregulation in rat atrial myocytes during heart failure. Circ Res 2001. 89(7):607-613.
110. Yang Y, Chen X, Margulies K, Jeevanandam V, Pollack P, Bailey BA, Houser SR. L-type Ca2+ channel alpha 1c subunit isoform switching in failing human ventricular myocardium. J Mol Cell Cardiol 2000. 32(6):973-984.
111. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004. 119(1):19-31.
112. Gomez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF, Cannell MB, McCune SA, Altschuld RA, Lederer WJ. Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 1997. 276(5313):800-806.
113. Beuckelmann DJ, Nabauer M, Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 1992. 85(3):1046-1055.
114. Beuckelmann DJ, Wier WG. Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Physiol 1988. 405:233-255.
115. Wier WG, Egan TM, Lopez-Lopez JR, Balke CW. Local control of excitation-contraction coupling in rat heart cells. J Physiol 1994. 474(3):463-471.
116. Hobai IA, O'Rourke B. Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure. Circulation 2001. 103(11):1577-1584.
117. Pogwizd SM, Schlotthauer K, Li L, Yuan W, Bers DM. Arrhythmogenesis and contractile dysfunction in heart failure: Roles of sodium-calcium exchange, inward rectifier potassium current, and residual beta-adrenergic responsiveness. Circ Res 2001. 88(11):1159-116.
118. Lindner M, Brandt MC, Sauer H, Hescheler J, Bohle T, Beuckelmann DJ. Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure. Cell Calcium 2002. 31(4):175-182.
119. Lindner M, Erdmann E, Beuckelmann DJ. Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol 1998. 30(4):743-749.
120. Sjaastad I, Wasserstrom JA, Sejersted OM. Heart failure – a challenge to our current concepts of excitation-contraction coupling. J Physiol 2003. 546:33-47.
121. Shorofsky SR, Aggarwal R, Corretti M, Baffa JM, Strum JM, Al-Seikhan BA, Kobayashi YM, Jones LR, Wier WG, Balke CW. Cellular mechanisms of altered contractility in the hypertrophied heart: big hearts, big sparks. Circ Res 1999. 84(4):424-434.
122. Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 2000. 101(4):365-376.
123. Reuter H, Han T, Motter C, Philipson KD, Goldhaber JI. Mice overexpressing the cardiac sodium-calcium exchanger: defects in excitation-contraction coupling. J Physiol 2004. 554:779-789.
124. Henderson SA, Goldhaber JI, So JM, Han T, Motter C, Ngo A, Chantawansri C, Ritter MR, Friedlander M, Nicoll DA, Frank JS, Jordan MC, Roos KP, Ross RS, Philipson KD. Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1. Circ Res 2004. 95(6):604-611.
125. Grandy SA, Denovan-Wright EM, Ferrier GR, Howlett SE. Overexpression of human beta2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes. Am J Physiol Heart Circ Physiol 2004. 287(3):H1029-H1038.