L-type CaV1.2 calcium channels: From in vitro findings to in vivo function

Physiological Reviews

Volumn 94, Issue 1, 2014, Pages 303-326

  Hofmann, Franz ^a,b   Flockerzi, Veit ^a,b   Kahl, Sabine ^a,b   Wegener, Jörg W ^a,b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM CHANNEL L TYPE; CALCIUM CHANNEL L TYPE 1.2; CALCIUM CHANNEL L TYPE BETA2; CALCIUM ION; PROTEIN KINASE; UNCLASSIFIED DRUG; CALCIUM; L TYPE CALCIUM CHANNEL ALPHA(1C); L-TYPE CALCIUM CHANNEL ALPHA(1C);

ARTICLE; BETA ADRENERGIC STIMULATION; BRAIN; ELECTROPHYSIOLOGY; GENE EXPRESSION SYSTEM; GENE INACTIVATION; GENE MUTATION; GENETIC CODE; GENETIC VARIABILITY; HETEROLOGOUS EXPRESSION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; KNOCKOUT MOUSE; MUTAGENESIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; PROTEIN STRUCTURE; PROTEIN SUBUNIT; REGULATORY MECHANISM; SMOOTH MUSCLE; SMOOTH MUSCLE CONTRACTILITY; UPREGULATION; ANIMAL; CHEMISTRY; GENETICS; KINETICS; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; REVIEW; SEQUENCE HOMOLOGY;

ANIMALS; CALCIUM; CALCIUM CHANNELS, L-TYPE; HUMANS; KINETICS; PHOSPHORYLATION; PROTEIN SUBUNITS; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 84891509120     PISSN: 00319333     EISSN: 15221210     Source Type: Journal    
DOI: 10.1152/physrev.00016.2013     Document Type: Article

References (327)

1. 2+ channel: perspectives for new pharmacological targets. J Pharmacol Exp Ther 300: 724-728, 2002.
2. Abiria SA, Colbran RJ. CaMKII associates with Ca(V)1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation. J Neurochem 112: 150-161, 2010.
3. 2+ channel intracellular linker: a structure-function analysis. J Neurosci 32: 7602-7613, 2012.
4. Altier C, Spaetgens RL, Nargeot J, Bourinet E, Zamponi GW. Multiple structural elements contribute to voltage-dependent facilitation of neuronal alpha 1C (CaV1.2) L-type calcium channels. Neuropharmacology 40: 1050-1057, 2001.
5. 2+ channels: is a unifying mechanism at hand? J Mol Cell Cardiol 33: 639-650, 2001.
6. 2+ current in rabbit ventricular myocytes. Circ Res 75: 854-861, 1994.
7. Angelotti T, Hofmann F. Tissue-specific expression of splice variants of the mouse voltage-gated calcium channel alpha2/delta subunit. FEBS Lett 397: 331-337, 1996.
8. Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B, Gelber P, Bonaros EP Jr, Burashnikov E, Wu Y, Sargent JD, Schickel S, Oberheiden R, Bhatia A, Hsu LF, Haissaguerre M, Schimpf R, Borggrefe M, Wolpert C. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 115: 442-449, 2007.
9. Arner A, Lofgren M, Morano I. Smooth, slow and smart muscle motors. J Muscle Res Cell Motil 24: 165-173, 2003.
10. Bader PL, Faizi M, Kim LH, Owen SF, Tadross MR, Alfa RW, Bett GC, Tsien RW, Rasmusson RL, Shamloo M. Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci USA 108: 15432-15437, 2011.
11. Badou A, Jha MK, Matza D, Mehal WZ, Freichel M, Flockerzi V, Flavell RA. Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function. Proc Natl Acad Sci USA 103: 15529-15534, 2006.
12. 2+ channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Proc Natl Acad Sci USA 103: 7500-7505, 2006.
13. 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 Visual Sci 43: 1595-1603, 2002.
14. 2+ (CaV1.2) channel C-terminus fragment is a bi-modal vasodilator. J Physiol 591: 2987-2998, 2013.
15. Bannister JP, Thomas-Gatewood CM, Neeb ZP, Adebiyi A, Cheng X, Jaggar JH. Ca(V)1.2 channel N-terminal splice variants modulate functional surface expression in resistance size artery smooth muscle cells. J Biol Chem 286: 15058-15066, 2011.
16. Barclay J, Balaguero N, Mione M, Ackerman SL, Letts VA, Brodbeck J, Canti C, Meir A, Page KM, Kusumi K, Perez-Reyes E, Lander ES, Frankel WN, Gardiner RM, Dolphin AC, Rees M. Ducky mouse phenotype of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells. J Neurosci 21: 6095-6104, 2001.
17. Barclay J, Rees M. Genomic organization of the mouse and human alpha2delta2 voltage-dependent calcium channel subunit genes. Mammalian Genome 11: 1142-1144, 2000.
18. Barrett CF, Tsien RW. The Timothy syndrome mutation differentially affects voltageand calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc Natl Acad Sci USA 105: 2157-2162, 2008.
19. Bauer EP, Schafe GE, LeDoux JE. NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. J Neurosci 22: 5239-5249, 2002.
20. 2+ channel Cav14alpha1 from mouse retina. Invest Ophthalmol Vis Sci 45: 708-713, 2004.
21. Bayliss WM. On the local reactions of the arterial wallto changes of internal pressure. J Physiol 28: 220-231, 1902.
22. Bengtson CP, Bading H. Nuclear calcium signaling. Adv Exp Med Biol 970: 377-405, 2012.
23. 2+ oscillation frequency and insulin exocytosis. Cell 119: 273-284, 2004.
24. 2+ channels exhibit unique regulation and functional roles in cardiomyocytes. J Mol Cell Cardiol 52: 376-387, 2012.
25. Bezanilla F. The voltage sensor in voltage-dependent ion channels. Physiol Rev 80: 555-592, 2000.
26. Bidaud I, Mezghrani A, Swayne LA, Monteil A, Lory P. Voltage-gated calcium channels in genetic diseases. Biochim Biophys Acta 1763: 1169-1174, 2006.
27. Biel M, Hullin R, Freundner S, Singer D, Dascal N, Flockerzi V, Hofmann F. Tissuespecific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels. Eur J Biochem 200: 81-88, 1991.
28. Biel M, Ruth P, Bosse E, Hullin R, Stuhmer W, Flockerzi V, Hofmann F. Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung. FEBS Lett 269: 409-412, 1990.
29. 2+ channel to EQ induces dilated cardiomyopathy and death. J Biol Chem 287: 22616-22625, 2012.
30. Blaich A, Welling A, Fischer S, Wegener JW, Kostner K, Hofmann F, Moosmang S. Facilitation of murine cardiac L-type Ca(v)1.2 channel is modulated by calmodulin kinase II-dependent phosphorylation of S1512 and S1570. Proc Natl Acad Sci USA 107: 10285-10289, 2010.
31. 2+ channel is up-regulated by protein kinase C. J Biol Chem 277: 3419-3423, 2002.
32. Bohn G, Moosmang S, Conrad H, Ludwig A, Hofmann F, Klugbauer N. Expression of T-and L-type calcium channel mRNA in murine sinoatrial node. FEBS Lett 481: 73-76, 2000.
33. Bosse E, Regulla S, Biel M, Ruth P, Meyer HE, Flockerzi V, Hofmann F. The cDNA and deduced amino acid sequence of the gamma subunit of the L-type calcium channel from rabbit skeletal muscle. FEBS Lett 267: 153-156, 1990.
34. Bourinet E, Charnet P, Tomlinson WJ, Stea A, Snutch TP, Nargeot J. Voltage-dependent facilitation of a neuronal alpha 1C L-type calcium channel. EMBO J 13: 5032-5039, 1994.
35. Brandmayr J, Poomvanicha M, Domes K, Ding J, Blaich A, Wegener JW, Moosmang S, Hofmann F. Deletion of the C-terminal phosphorylation sites in the cardiac betasubunit does not affect the basic beta-adrenergic response of the heart and the Ca(v)1.2 channel. J Biol Chem 287: 22584-22592, 2012.
36. Braun M, Ramracheya R, Johnson PR, Rorsman P. Exocytotic properties of human pancreatic beta-cells. Mech Exocytosis 1152: 187-193, 2009.
37. Brill J, Klocke R, Paul D, Boison D, Gouder N, Klugbauer N, Hofmann F, Becker CM, Becker K. entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse. J Biol Chem 279: 7322-7330, 2004.
38. Bunemann M, Gerhardstein BL, Gao T, Hosey MM. Functional regulation of L-type calcium channels via protein kinase A-mediated phosphorylation of the beta(2) subunit. J Biol Chem 274: 33851-33854, 1999.
39. 2+ channels. Physiol Rev 90: 1461-1506, 2010.
40. Burashnikov E, Pfeiffer R, Barajas-Martinez H, Delpon E, Hu D, Desai M, Borggrefe M, Haissaguerre M, Kanter R, Pollevick GD, Guerchicoff A, Laino R, Marieb M, Nademanee K, Nam GB, Robles R, Schimpf R, Stapleton DD, Viskin S, Winters S, Wolpert C, Zimmern S, Veltmann C, Antzelevitch C. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm 7: 1872-1882, 2010.
41. 2+ channel subunit compositions in lethargic mouse brain. Mol Cell Neurosci 13: 293-311, 1999.
42. 2+ channel gamma subunit genes on chromosome 19q13.4: evolution and expression profile of the gamma subunit gene family. Genomics 71: 339-350, 2001.
43. 2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 88: 385-392, 1997.
44. 2+ channel isoforms in the extinction of conditioned fear. Learn Mem 15: 378-386, 2008.
45. Cain CK, Godsil BP, Jami S, Barad M. The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice. Learn Mem 12: 277-284, 2005.
46. 2+ channel alpha(2)delta-1 auxiliary subunit. Cell Calcium 51: 22-30, 2012.
47. Castellano A, Wei X, Birnbaumer L, Perez-Reyes E. Cloning and expression of a third calcium channel beta subunit. J Biol Chem 268: 3450-3455, 1993.
48. 2+ channels. Annu Rev Cell Dev Biol 16: 521-555, 2000.
49. Catterall WA. Voltage-gated calcium channels. Cold Spring Harbor Perspect Biol 3: a003947, 2011.
50. Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57: 411-425, 2005.
51. Chang FC, Hosey MM. Dihydropyridine and phenylalkylamine receptors associated with cardiac and skeletal muscle calcium channels are structurally different. J Biol Chem 263: 18929-18937, 1988.
52. Chen RS, Deng TC, Garcia T, Sellers ZM, Best PM. Calcium channel gamma subunits: a functionally diverse protein family. Cell Biochem Biophys 47: 178-186, 2007.
53. 2+ channels. Nature 429: 675-680, 2004.
54. Cheng X, Liu J, Asuncion-Chin M, Blaskova E, Bannister JP, Dopico AM, Jaggar JH. A novel Ca(V)1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits. J Biol Chem 282: 29211-29221, 2007.
55. 2+ channels. Neuroscience 120: 435-442, 2003.
56. Cohen-Kutner M, Yahalom Y, Trus M, Atlas D. Calcineurin controls voltage-dependent-inactivation (VDI) of the normal and Timothy cardiac channels. Scientific Reports 2: 2012.
57. 2+ channel beta subunits revealed by their expression in adult rat heart cells. J Physiol 541: 435-452, 2002.
58. 2+ channel Cav1.2. Science 293: 98-101, 2001.
59. Davies A, Hendrich J, Van Minh AT, Wratten J, Douglas L, Dolphin AC. Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels. Trends Pharmacol Sci 28: 220-228, 2007.
60. Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 79: 387-423, 1999.
61. Davis SE, Bauer EP. L-type voltage-gated calcium channels in the basolateral amygdala are necessary for fear extinction. J Neurosci 32: 13582-13586, 2012.
62. De Jongh KS, Murphy BJ, Colvin AA, Hell JW, Takahashi M, Catterall WA. Specific phosphorylation of a site in the full-length form of the alpha 1 subunit of the cardiac L-type calcium channel by adenosine 3',5'-cyclic monophosphate-dependent protein kinase. Biochemistry 35: 10392-10402, 1996.
63. 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 265: 14738-14741, 1990.
64. De Jongh KS, Warner C, Colvin AA, Catterall WA. Characterization of the two size forms of the alpha 1 subunit of skeletal muscle L-type calcium channels. Proc Natl Acad Sci USA 88: 10778-10782, 1991.
65. Defelice LJ. Molecular and biophysical view of the Ca channel: a hypothesis regarding oligomeric structure, channel clustering, and macroscopic current. J Membr Biol 133: 191-202, 1993.
66. 2+ influx. Embo J 22: 4337-4345, 2003.
67. Ding J, Domes K, Hofmann F, Wegener JW. Truncation of murine Ca(V)1.2 at Asp 1904 increases Ca(V)1.3 expression in embryonic atrial cardiomyocytes. Pflügers Arch 2013.
68. 2+ signaling amplification by oligomerization of L-type Cav1.2 channels Proc Natl Acad Sci USA 109: 1749-1754, 2012.
69. Dolphin AC. Calcium channel auxiliary alpha2delta and beta subunits: trafficking and one step beyond. Nat Rev Neurosci 13: 542-555, 2012.
70. Dolphin AC. Calcium channel diversity: multiple roles of calcium channel subunits. Curr Opin Neurobiol 19: 237-244, 2009.
71. Domes K, Ding J, Lemke T, Blaich A, Wegener JW, Brandmayr J, Moosmang S, Hofmann F. Truncation of murine CaV1.2 at Asp-1904 results in heart failure after birth. J Biol Chem 286: 33863-33871, 2011.
72. Douglas WW. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol 34: 451-474, 1968.
73. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280: 69-77, 1998.
74. Dzhura I, Wu Y, Colbran RJ, Balser JR, Anderson ME. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol 2: 173-177, 2000.
75. 2+ channel beta4 genes in 13 vertebrate species. Physiol Genomics 35: 133-144, 2008.
76. 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 241: 1661-1664, 1988.
77. Enes J, Langwieser N, Ruschel J, Carballosa-Gonzalez MM, Klug A, Traut MH, Ylera B, Tahirovic S, Hofmann F, Stein V, Moosmang S, Hentall ID, Bradke F. Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons. Curr Biol 20: 1154-1164, 2010.
78. Eroglu C, Allen NJ, Susman MW, O'Rourke NA, Park CY, Ozkan E, Chakraborty C, Mulinyawe SB, Annis DS, Huberman AD, Green EM, Lawler J, Dolmetsch R, Garcia KC, Smith SJ, Luo ZD, Rosenthal A, Mosher DF, Barres BA. Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell 139: 380-392, 2009.
79. Ertel EA, Campbell KP, Harpold MM, Hofmann F, Mori Y, Perez-Reyes E, Schwartz A, Snutch TP, Tanabe T, Birnbaumer L, Tsien RW, Catterall WA. Nomenclature of voltage-gated calcium channels. Neuron 25: 533-535, 2000.
80. Erxleben C, Liao YH, Gentile S, Chin D, Gomez-Alegria C, Mori Y, Birnbaumer L, Armstrong DL. Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. Proc Natl Acad Sci USA 103: 3932-3937, 2006.
81. 2+ sparks in murine arterial smooth muscle cells. J Physiol 584: 205-219, 2007.
82. 2+ current in guinea-pig myocytes. J Physiol 405: 461-475, 1988.
83. 2+ release in arterial smooth muscle. Circ Res 106: 1285-1289, 2010.
84. 2+ channels: new mechanism for depolarization-evoked mammalian arterial contraction. Circ Res 108: 1348-1357, 2011.
85. Ferreira G, Yi J, Rios E, Shirokov R. Ion-dependent inactivation of barium current through L-type calcium channels. J Gen Physiol 109: 449-461, 1997.
86. Ferreira MA, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, Fan J, Kirov G, Perlis RH, Green EK, Smoller JW, Grozeva D, Stone J, Nikolov I, Chambert K, Hamshere ML, Nimgaonkar VL, Moskvina V, Thase ME, Caesar S, Sachs GS, Franklin J, Gordon-Smith K, Ardlie KG, Gabriel SB, Fraser C, Blumenstiel B, Defelice M, Breen G, Gill M, Morris DW, Elkin A, Muir WJ, McGhee KA, Williamson R, MacIntyre DJ, MacLean AW, St CD, Robinson M, Van Beck M, Pereira AC, Kandaswamy R, Mc-Quillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Ferrier IN, Anjorin A, Farmer A, Curtis D, Scolnick EM, McGuffin P, Daly MJ, Corvin AP, Holmans PA, Blackwood DH, Gurling HM, Owen MJ, Purcell SM, Sklar P, Craddock N, Wellcome Trust Case Control. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 40: 1056-1058, 2008.
87. Ferry DR, Glossmann H. Identification of putative calcium channels in skeletal-muscle microsomes. FEBS Lett 148: 331-337, 1982.
88. Findeisen F, Minor DL Jr. Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation. J Gen Physiol 133: 327-343, 2009.
89. Fischmeister R, Castro L, Abi-Gerges A, Rochais F, Vandecasteele G. Species-and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels. Comp Biochem Physiol A Mol Integr Physiol 142: 136-143, 2005.
90. Fisher SA. Vascular smooth muscle phenotypic diversity and function. Physiol Gen 42A: 169-187, 2010.
91. Flockerzi V, Oeken HJ, Hofmann F, Pelzer D, Cavalie A, Trautwein W. Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Nature 323: 66-68, 1986.
92. Foell JD, Balijepalli RC, Delisle BP, Yunker AM, Robia SL, Walker JW, McEnery MW, January CT, Kamp TJ. Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization. Physiol Gen 17: 183-200, 2004.
93. 2+ channel in skeletal muscle. Eur J Pharmacol 86: 141-142, 1982.
94. 2+ currents and alters channel inactivation properties. J Biol Chem 275: 14476-14481, 2000.
95. Fu Y, Westenbroek RE, Yu FH, Clark JP 3rd, Marshall MR, Scheuer T, Catterall WA. Deletion of the distal C terminus of CaV1.2 channels leads to loss of beta-adrenergic regulation and heart failure in vivo. J Biol Chem 286: 12617-12626, 2011.
96. Fukuyama M, Ohno S, Wang Q, Kimura H, Makiyama T, Itoh H, Ito M, Horie M. L-type calcium channel mutations in Japanese patients with inherited arrhythmias. Circ J 77: 1799-1806, 2013.
97. Fuller-Bicer GA, Varadi G, Koch SE, Ishii M, Bodi I, Kadeer N, Muth JN, Mikala G, Petrashevskaya NN, Jordan MA, Zhang SP, Qin N, Flores CM, Isaacsohn I, Varadi M, Mori Y, Jones WK, Schwartz A. Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol 297: H117-H124, 2009.
98. Fuller MD, Emrick MA, Sadilek M, Scheuer T, Catterall WA. Molecular mechanism of calcium channel regulation in the fight-or-flight response. Sci Signal 3: ra70, 2010.
99. Gandia L, Mayorgas I, Michelena P, Cuchillo I, de Pascual R, Abad F, Novalbos JM, Larranaga E, Garcia AG. Human adrenal chromaffin cell calcium channels: drastic current facilitation in cell clusters, but not in isolated cells. Pflügers Arch 436: 696-704, 1998.
100. 2+ channels in cardiac myocytes requires the distal carboxyl terminus of alpha1C but not serine 1928. Circ Res 98: e11-18, 2006.
101. 2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits. Neuron 19: 185-196, 1997.
102. Garcia AG, Garcia-De-Diego AM, Gandia L, Borges R, Garcia-Sancho J. Calcium signaling and exocytosis in adrenal chromaffin cells. Physiol Rev 86: 1093-1131, 2006.
103. Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem 271: 5768-5776, 1996.
104. Gerhardstein BL, Gao T, Bunemann M, Puri TS, Adair A, Ma H, Hosey MM. Proteolytic processing of the C terminus of the alpha(1C) subunit of L-type calcium channels and the role of a proline-rich domain in membrane tethering of proteolytic fragments. J Biol Chem 275: 8556-8563, 2000.
105. Gerhardstein BL, Puri TS, Chien AJ, Hosey MM. Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium channels. Biochemistry 38: 10361-10370, 1999.
106. Gidhjain M, Huang BY, Jain P, Battula V, Elsherif N. Reemergence of the fetal pattern of L-type calcium-channel gene-expression in noninfarcted myocardium during leftventricular remodeling. Biochem Biophys Res Commun 216: 892-897, 1995.
107. Glossmann H, Ferry DR, Lubbecke F, Mewes R, Hofmann F. Calcium channels: direct identification with radioligand binding studies. Trends Pharmacol Sci 3: 431-437, 1982.
108. 2+ channels. Positive allosteric heterotropic regulation by D-cis-diltiazem is associated with apparent channel oligomer dissociation. FEBS Lett 157: 63-69, 1983.
109. Gomez-Ospina N, Tsuruta F, Barreto-Chang O, Hu L, Dolmetsch R. The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor. Cell 127: 591-606, 2006.
110. Gong HC, Hang J, Kohler W, Li L, Su TZ. Tissue-specific expression and gabapentinbinding properties of calcium channel alpha2delta subunit subtypes. J Membr Biol 184: 35-43, 2001.
111. 2+ channel activity induces hypertrophy and heart failure in mice. J Clin Invest 122: 280-290, 2012.
112. Gray PC, Tibbs VC, Catterall WA, Murphy BJ. Identification of a 15-kDa cAMPdependent protein kinase-anchoring protein associated with skeletal muscle L-type calcium channels. J Biol Chem 272: 6297-6302, 1997.
113. 2+ channel facilitation mediated by phosphorylation of the beta subunit by CaMKII. Mol Cell 23: 641-650, 2006.
114. Haase H, Bartel S, Karczewski P, Morano I, Krause EG. In-vivo phosphorylation of the cardiac L-type calcium channel beta-subunit in response to catecholamines. Mol Cell Biochem 164: 99-106, 1996.
115. Haase H, Karczewski P, Beckert R, Krause EG. Phosphorylation of the L-type calcium channel beta subunit is involved in beta-adrenergic signal transduction in canine myocardium. FEBS Lett 335: 217-222, 1993.
116. 2+ channel subunits during cardiac ontogeny in mice and rats: identification of fetal alpha(1C) and beta subunit isoforms. J Cell Biochem 76: 695-703, 2000.
117. Haddock RE, Hill CE. Rhythmicity in arterial smooth muscle. J Physiol 566: 645-656, 2005.
118. Hall DD, Davare MA, Shi M, Allen ML, Weisenhaus M, McKnight GS, Hell JW. Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons. Biochemistry 46: 1635-1646, 2007.
119. Hall DD, Feekes JA, Arachchige Don AS, Shi M, Hamid J, Chen L, Strack S, Zamponi GW, Horne MC, Hell JW. Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation. Biochemistry 45: 3448-3459, 2006.
120. 2+ channels by calmodulin. Sci STKE 2006: er1, 2006.
121. Hamshere ML, Walters JTR, Smith R, Richards AL, Green E, Grozeva D, Jones I, Forty L, Jones L, Gordon-Smith K, Riley B, O'Neill T, Kendler KS, Sklar P, Purcell S, Kranz J, Morris D, Gill M, Holmans P, Craddock N, Corvin A, Owen MJ, O'Donovan MC. Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 18: 708-712, 2013.
122. Hansen JP, Chen RS, Larsen JK, Chu PJ, Janes DM, Weis KE, Best PM. Calcium channel gamma6 subunits are unique modulators of low voltage-activated (Cav3.1) calcium current. J Mol Cell Cardiol 37: 1147-1158, 2004.
123. 2+ channel currents and contraction in CaVbeta3-deficient ileum smooth muscle from mouse. Cell Calcium 42: 477-487, 2007.
124. Hell JW, Westenbroek RE, Warner C, Ahlijanian MK, Prystay W, Gilbert MM, Snutch TP, Catterall WA. Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J Cell Biol 123: 949-962, 1993.
125. Hell JW, Yokoyama CT, Wong ST, Warner C, Snutch TP, Catterall WA. Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel alpha 1 subunit. J Biol Chem 268: 19451-19457, 1993.
126. Helton TD, Xu W, Lipscombe D. Neuronal L-type calcium channels open quickly and are inhibited slowly. J Neurosci 25: 10247-10251, 2005.
127. 2+ channels. J Physiol 528: 237-249, 2000.
128. Herzig S, Khan IF, Grundemann D, Matthes J, Ludwig A, Michels G, Hoppe UC, Chaudhuri D, Schwartz A, Yue DT, Hullin R. Mechanism of Ca(v)1.2 channel modulation by the amino terminus of cardiac beta2-subunits. FASEB J 21: 1527-1538, 2007.
129. 2+-channels: contribution of Ca(V)1.3 and Ca(V)1.2 isoforms. Neuroscience 139: 1005-1015, 2006.
130. 2+-channel beta 4 subunit. Proc Natl Acad Sci USA 100: 307-312, 2003.
131. Hill-Eubanks DC, Werner ME, Heppner TJ, Nelson MT. Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol 3: a004549, 2011.
132. 2+ channel diversity. Annu Rev Neurosci 17: 399-418, 1994.
133. Hofmann F, Lacinova L, Klugbauer N. Voltage-dependent calcium channels: from structure to function. Rev Physiol Biochem Pharmacol 139: 33-87, 1999.
134. Hryshko LV, Bers DM. Ca current facilitation during postrest recovery depends on Ca entry. Am J Physiol Heart Circ Physiol 259: H951-H961, 1990.
135. 2+ signals for facilitation. J Cell Biol 171: 537-547, 2005.
136. 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 278: 21623-21630, 2003.
137. 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 11: 885-890, 1992.
138. 2+ channel and modulates its function. J Biol Chem 277: 4079-4087, 2002.
139. Hulme JT, Westenbroek RE, Scheuer T, Catterall WA. Phosphorylation of serine 1928 in the distal C-terminal domain of cardiac CaV1.2 channels during beta1-adrenergic regulation. Proc Natl Acad Sci USA 103: 16574-16579, 2006.
140. Hulme JT, Yarov-Yarovoy V, Lin TW, Scheuer T, Catterall WA. Autoinhibitory control of the CaV1.2 channel by its proteolytically processed distal C-terminal domain. J Physiol 576: 87-102, 2006.
141. Huster M, Frei E, Hofmann F, Wegener JW. A complex of Ca(V)1.2/PKC is involved in muscarinic signaling in smooth muscle. FASEB J 24: 2651-2659, 2010.
142. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR, Wigler M. De novo gene disruptions in children on the autistic spectrum. Neuron 74: 285-299, 2012.
143. 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 165: 1007-1018, 2004.
144. Jay SD, Ellis SB, McCue AF, Williams ME, Vedvick TS, Harpold MM, Campbell KP. Primary structure of the gamma subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 248: 490-492, 1990.
145. 2+ channels in ACC. Nat Neurosci 13: 482-488, 2010.
146. Jha MK, Badou A, Meissner M, McRory JE, Freichel M, Flockerzi V, Flavell RA. Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels. Nature Immunol 10: 1275-1282, 2009.
147. 2+/calmodulin-dependent protein kinase II bound to the C-terminal domain. Proc Natl Acad Sci USA 105: 341-346, 2008.
148. 2+ channels in skeletal muscle cells requires anchored cAMP-dependent protein kinase. Proc Natl Acad Sci USA 91: 11492-11496, 1994.
149. Jones BW, Brunet S, Gilbert ML, Nichols CB, Su T, Westenbroek RE, Scott JD, Catterall WA, McKnight GS. Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation. Proc Natl Acad Sci USA 109: 17099-17104, 2012.
150. Jurik A, Fischer S, Thoringer C, Wotjak C, Moosmang S. The IQ motif of the L-type channel Ca(v)1.2 plays a role in mood disorders. Naunyn-Schmiedebergs Arch Pharmacol 383: 31, 2011.
151. Kameyama M, Hescheler J, Hofmann F, Trautwein W. Modulation of Ca current during the phosphorylation cycle in the guinea pig heart. Pflügers Arch 407: 123-128, 1986.
152. Kamp TJ, Hell JW. Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ Res 87: 1095-1102, 2000.
153. Kandel ER. The molecular biology of memory storage: a dialogue between genes and synapses. Science 294: 1030-1038, 2001.
154. 2+ channels. J Biol Chem 276: 32917-32924, 2001.
155. 2+ channels in rat islet beta-cells. Pflügers Arch 435: 578-580, 1998.
156. Kato AS, Zhou W, Milstein AD, Knierman MD, Siuda ER, Dotzlaf JE, Yu H, Hale JE, Nisenbaum ES, Nicoll RA, Bredt DS. New transmembrane AMPA receptor regulatory protein isoform, gamma-7, differentially regulates AMPA receptors. J Neurosci 27: 4969-4977, 2007.
157. 2+ channels [Ca(V)1.2a, b] by protein kinases. Am J Physiol Cell Physiol 281: C1743-C1756, 2001.
158. Kim HL, Kim H, Lee P, King RG, Chin H. Rat brain expresses an alternatively spliced form of the dihydropyridine-sensitive L-type calcium channel alpha 2 subunit. Proc Natl Acad Sci USA 89: 3251-3255, 1992.
159. 2+ channels. Neuron 41: 745-754, 2004.
160. 2+ channels expressed in CHO cells. EMBO J 13: 2502-2507, 1994.
161. Klugbauer N, Dai S, Specht V, Lacinova L, Marais E, Bohn G, Hofmann F. A family of gamma-like calcium channel subunits. FEBS Lett 470: 189-197, 2000.
162. Klugbauer N, Marais E, Hofmann F. Calcium channel alpha2delta subunits: differential expression, function, and drug binding. J Bioenerget Biomembr 35: 639-647, 2003.
163. Koval OM, Guan XQ, Wu YJ, Joiner ML, Gao Z, Chen BY, Grumbach IM, Luczak ED, Colbran RJ, Song LS, Hund TJ, Mohler PJ, Anderson ME. Ca-V 1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proc Natl Acad Sci USA 107: 4996-5000, 2010.
164. Kuhbandner S, Brummer S, Metzger D, Chambon P, Hofmann F, Feil R. Temporally controlled somatic mutagenesis in smooth muscle. Genesis 28: 15-22, 2000.
165. 2+ channel subunits beta3 or beta4. Channels 3: 366-376, 2009.
166. 2+ channel in rat pheochromocytoma cells: 2 sets of ion-binding sites in the pore. J Physiol 466: 629-655, 1993.
167. 2+-channel functions. Nat Neurosci 12: 1415-1423, 2009.
168. Lacinova L, Klugbauer N, Hofmann F. State-and isoform-dependent interaction of isradipine with the alpha(1C) L-type calcium channel. Pflügers Arch 440: 50-60, 2000.
169. Lai Y, Seagar MJ, Takahashi M, Catterall WA. Cyclic AMP-dependent phosphorylation of two size forms of alpha 1 subunits of L-type calcium channels in rat skeletal muscle cells. J Biol Chem 265: 20839-20848, 1990.
170. 2+ channel beta subunit depletion in nodosus ganglion neurons. J Neurosci 17: 6621-6628, 1997.
171. Langwieser N, Christel CJ, Kleppisch T, Hofmann F, Wotjak CT, Moosmang S. Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels. J Neurosci 30: 8367-8375, 2010.
172. Leach RN, Brickley K, Norman RI. Cyclic AMP-dependent protein kinase phosphorylates residues in the C-terminal domain of the cardiac L-type calcium channel alpha1 subunit. Biochim Biophys Acta 1281: 205-212, 1996.
173. Lee AS, Ra S, Rajadhyaksha AM, Britt JK, De Jesus-Cortes H, Gonzales KL, Lee A, Moosmang S, Hofmann F, Pieper AA, Rajadhyaksha AM. Forebrain elimination of cacna1c mediates anxiety-like behavior in mice. Mol Psychiatry 17: 1054-1055, 2012.
174. Lee KS. Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization. Proc Natl Acad Sci USA 84: 3941-3945, 1987.
175. Lee TS, Karl R, Moosmang S, Lenhardt P, Klugbauer N, Hofmann F, Kleppisch T, Welling A. Calmodulin kinase II is involved in voltage-dependent facilitation of the L-type Cav1.2 calcium channel: Identification of the phosphorylation sites. J Biol Chem 281: 25560-25567, 2006.
176. Lemke T, Welling A, Christel CJ, Blaich A, Bernhard D, Lenhardt P, Hofmann F, Moosmang S. Unchanged beta-adrenergic stimulation of cardiac L-type calcium channels in Cav1.2 phosphorylation site S1928A mutant mice. J Biol Chem 283: 34738-34744, 2008.
177. Li CY, Zhang XL, Matthews EA, Li KW, Kurwa A, Boroujerdi A, Gross J, Gold MS, Dickenson AH, Feng G, Luo ZD. Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation. Pain 125: 20-34, 2006.
178. 2+. J Membr Biol 233: 23-33, 2010.
179. Liao P, Li G, Yu de J, Yong TF, Wang JJ, Wang J, Soong TW. Molecular alteration of Ca(v)1.2 calcium channel in chronic myocardial infarction. Pflügers Arch 458: 701-711, 2009.
180. Liao P, Yu D, Lu S, Tang Z, Liang MC, Zeng S, Lin W, Soong TW. Smooth muscleselective alternatively spliced exon generates functional variation in Cav1.2 calcium channels. J Biol Chem 279: 50329-50335, 2004.
181. Link S, Meissner M, Held B, Beck A, Weissgerber P, Freichel M, Flockerzi V. Diversity and developmental expression of L-type calcium channel beta2 proteins and their influence on calcium current in murine heart. J Biol Chem 284: 30129-30137, 2009.
182. Lorenzon NM, Beam KG. Disease causing mutations of calcium channels. Channels 2: 163-179, 2008.
183. Ludwig A, Flockerzi V, Hofmann F. Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain. J Neurosci 17: 1339-1349, 1997.
184. Ma H, Groth RD, Wheeler DG, Barrett CF, Tsien RW. Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation. Neurosci Res 70: 2-8, 2011.
185. Mahapatra S, Marcantoni A, Zuccotti A, Carabelli V, Carbone E. Equal sensitivity of Cav1.2 and Cav13 channels to the opposing modulations of PKA and PKG in mouse chromaffin cells. J Physiol 590: 5053-5073, 2012.
186. Maier LS, Bers DM. Calcium, calmodulin, and calcium-calmodulin kinase II: heartbeat to heartbeat and beyond. J Mol Cell Cardiol 34: 919-939, 2002.
187. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron 44: 5-21, 2004.
188. Marcantoni A, Vandael DHF, Mahapatra S, Carabelli V, Sinnegger-Brauns MJ, Striessnig J, Carbone E. Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. J Neurosci 30: 491-504, 2010.
189. Marshall MR, Clark JP, 3rd Westenbroek R, Yu FH, Scheuer T, Catterall WA. Functional roles of a C-terminal signaling complex of CaV1 channels and A-kinase anchoring protein 15 in brain neurons. J Biol Chem 286: 12627-12639, 2011.
190. Martin-Moutot N, Leveque C, Sato K, Kato R, Takahashi M, Seagar M. Properties of omega conotoxin MVIIC receptors associated with alpha 1A calcium channel subunits in rat brain. FEBS Lett 366: 21-25, 1995.
191. Martin SJ, Morris RG. New life in an old idea: the synaptic plasticity and memory hypothesis revisited. Hippocampus 12: 609-636, 2002.
192. McDonald TF, Cavalie A, Trautwein W, Pelzer D. Voltage-dependent properties of macroscopic and elementary calcium channel currents in guinea pig ventricular myocytes. Pflügers Arch 406: 437-448, 1986.
193. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev 74: 365-507, 1994.
194. McEnery MW, Copeland TD, Vance CL. Altered expression and assembly of N-type calcium channel alpha1B and beta subunits in epileptic lethargic (lh/lh) mouse. J Biol Chem 273: 21435-21438, 1998.
195. McEnery MW, Snowman AM, Sharp AH, Adams ME, Snyder SH. Purified omegaconotoxin GVIA receptor of rat brain resembles a dihydropyridine-sensitive L-type calcium channel. Proc Natl Acad Sci USA 88: 11095-11099, 1991.
196. McKinney BC, Sze W, White JA, Murphy GG. L-type voltage-gated calcium channels in conditioned fear: a genetic and pharmacological analysis. Learning Memory 15: 326-334, 2008.
197. 2+ as the charge-carrier. J Physiol 483P:-P13, 1995.
198. Meissner M, Weissgerber P, Londono JE, Prenen J, Link S, Ruppenthal S, Molkentin JD, Lipp P, Nilius B, Freichel M, Flockerzi V. Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the cacnb2 gene. J Biol Chem 286: 15875-15882, 2011.
199. 2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci USA 88: 1197-1201, 1991.
200. 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 185: 95-109, 1998.
201. Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, Narumiya S, Numa S. Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium-channel. Nature 340: 230-233, 1989.
202. Mitterdorfer J, Froschmayr M, Grabner M, Moebius FF, Glossmann H, Striessnig J. Identification of PK-A phosphorylation sites in the carboxyl terminus of L-type calcium channel alpha 1 subunits. Biochemistry 35: 9400-9406, 1996.
203. 2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci 25: 9883-9892, 2005.
204. Moosmang S, Kleppisch T, Wegener J, Welling A, Hofmann F. Analysis of calcium channels by conditional mutagenesis. Handb Exp Pharmacol 469-490, 2007.
205. Moosmang S, Lenhardt P, Haider N, Hofmann F, Wegener JW. Mouse models to study L-type calcium channel function. Pharmacol Ther 106: 347-355, 2005.
206. Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, Hofmann F, Klugbauer N. Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood pressure regulation. EMBO J 22: 6027-6034, 2003.
207. Muller CS, Haupt A, Bildl W, Schindler J, Knaus HG, Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B, Schulte U. Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain. Proc Natl Acad Sci USA 107: 14950-14957, 2010.
208. 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 277: 40342-40351, 2002.
209. 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 36 Suppl 2: S69-73, 2000.
210. 2+ channel beta3 subunit. J Biol Chem 278: 43261-43267, 2003.
211. Murthy KS. Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol 68: 345-374, 2006.
212. 2+-dependent transgenic model of cardiac hypertrophy: a role for protein kinase Calpha. Circulation 103: 140-147, 2001.
213. 2+) channel in transgenic mice. Loss of isoproterenolinduced contraction. J Biol Chem 274: 21503-21506, 1999.
214. Nakai J, Adams BA, Imoto K, Beam KG. Critical roles of the S3 segment and S3-S4 linker of repeat-I in activation of L-type calcium channels. Proc Natl Acad Sci USA 91: 1014-1018, 1994.
215. 2+) channel alpha(1D) subunit in postnatal pancreatic beta cell generation. J Clin Invest 108: 1015-1022, 2001.
216. 2+ channels in neurons. Proc Natl Acad Sci USA 95: 12010-12015, 1998.
217. Napolitano C, Antzelevitch C. Phenotypical manifestations of mutations in the genes encoding subunits of the cardiac voltage-dependent L-type calcium channel. Circ Res 108: 607-618, 2011.
218. Nichols CB, Rossow CF, Navedo MF, Westenbroek RE, Catterall WA, Santana LF, McKnight GS. Sympathetic stimulation of adult cardiomyocytes requires association of AKAP5 with a subpopulation of L-type calcium channels. Circ Res 107: 747-756, 2010.
219. Noble S, Shimoni Y. Voltage-dependent potentiation of the slow inward current in frog atrium. J Physiol 310: 77-95, 1981.
220. Nystoriak MA, Murakami K, Penar PL, Wellman GC. Ca(v)1.2 splice variant with exon 9*is critical for regulation of cerebral artery diameter. Am J Physiol Heart Circ Physiol 297: H1820-H1828, 2009.
221. Ohrtman J, Ritter B, Polster A, Beam KG, Papadopoulos S. Sequence differences in the IQ motifs of CaV1.1 and CaV12 strongly impact calmodulin binding and calciumdependent inactivation. J Biol Chem 283: 29301-29311, 2008.
222. 2+ channels. J Neurosci 32: 15328-15337, 2012.
223. Opatowsky Y, Chen CC, Campbell KP, Hirsch JA. Structural analysis of the voltagedependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. Neuron 42: 387-399, 2004.
224. 2+ current. Nature 298: 576-578, 1982.
225. 2+ channel alpha 1C subunit. FEBS Lett 384: 189-192, 1996.
226. Perez-Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83: 117-161, 2003.
227. Perez-Reyes E, Castellano A, Kim HS, Bertrand P, Baggstrom E, Lacerda AE, Wei XY, Birnbaumer L. Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. J Biol Chem 267: 1792-1797, 1992.
228. Perez-Reyes E, Yuan W, Wei X, Bers DM. Regulation of the cloned L-type cardiac calcium channel by cyclic-AMP-dependent protein kinase. FEBS Lett 342: 119-123, 1994.
229. 2+-dependent inactivation of L-type calcium channels. Neuron 22: 549-558, 1999.
230. 2+ channels. J Biol Chem 272: 13877-13882, 1997.
231. Pietrobon D, Hess P. Novel mechanism of voltage-dependent gating in L-type calcium channels. Nature 346: 651-655, 1990.
232. 2+ channels. J Biol Chem 276: 30794-30802, 2001.
233. Platano D, Qin N, Noceti F, Birnbaumer L, Stefani E, Olcese R. Expression of the alpha(2)delta subunit interferes with prepulse facilitation in cardiac L-type calcium channels. Biophys J 78: 2959-2972, 2000.
234. 2+ channels. Cell 102: 89-97, 2000.
235. 2+-dependent inactivation are modified by mutation of the Ca(v)1.2 channel IQ motif. J Biol Chem 286: 26702-26707, 2011.
236. 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 368: 67-70, 1994.
237. Puri TS, Gerhardstein BL, Zhao XL, Ladner MB, Hosey MM. Differential effects of subunit interactions on protein kinase A-and C-mediated phosphorylation of L-type calcium channels. Biochemistry 36: 9605-9615, 1997.
238. 2+ channel depends on calmodulin. Proc Natl Acad Sci USA 96: 2435-2438, 1999.
239. 2+ channel beta subunit caused by palmitoylation. Proc Natl Acad Sci USA 95: 4690-4695, 1998.
240. 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 62: 485-496, 2002.
241. 2+ channel in the rat heart. Pediatr Res 69: 479-484, 2011.
242. Reinbothe TM, Alkayyali S, Ahlqvist E, Tuomi T, Isomaa B, Lyssenko V, Renstrom E. The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes. Diabetologia 56: 340-349, 2013.
243. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569-574, 1983.
244. Reuter H. Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J Physiol 242: 429-451, 1974.
245. Reuter H. Properties of two inward membrane currents in the heart. Annu Rev Physiol 41: 413-424, 1979.
246. Rosati B, Yan Q, Lee MS, Liou SR, Ingalls B, Foell J, Kamp TJ, McKinnon D. Robust L-type calcium current expression following heterozygous knockout of the Cav1.2 gene in adult mouse heart. J Physiol 589: 3275-3288, 2011.
247. Ross J Jr, Miura T, Kambayashi M, Eising GP, Ryu KH. Adrenergic control of the force-frequency relation. Circulation 92: 2327-2332, 1995.
248. Ruth P, Rohrkasten A, Biel M, Bosse E, Regulla S, Meyer HE, Flockerzi V, Hofmann F. Primary structure of the beta subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 245: 1115-1118, 1989.
249. Safayhi H, Haase H, Kramer U, Bihlmayer A, Roenfeldt M, Ammon HP, Froschmayr M, Cassidy TN, Morano I, Ahlijanian MK, Striessnig J. L-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells. Mol Endocrinol 11: 619-629, 1997.
250. Sanders KM. Regulation of smooth muscle excitation and contraction. Neurogastroenterol Motil 20 Suppl 1: 39-53, 2008.
251. Sather WA, McCleskey EW. Permeation and selectivity in calcium channels. Annu Rev Physiol 65: 133-159, 2003.
252. 2+ channels mediate cocaine-induced GluA1 trafficking in the nucleus accumbens, a longterm adaptation dependent on ventral tegmental area Ca(v)1.3 channels. J Neurosci 31: 13562-13575, 2011.
253. Schlick B, Flucher BE, Obermair GJ. Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167: 786-798, 2010.
254. Scholl UI, Goh G, Stolting G, de Oliveira RC, Choi M, Overton JD, Fonseca AL, Korah R, Starker LF, Kunstman JW, Prasad ML, Hartung EA, Mauras N, Benson MR, Brady T, Shapiro JR, Loring E, Nelson-Williams C, Libutti SK, Mane S, Hellman P, Westin G, Akerstrom G, Bjorklund P, Carling T, Fahlke C, Hidalgo P, Lifton RP. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet. In press.
255. Schroder E, Byse M, Satin J. L-type calcium channel C terminus autoregulates transcription. Circ Res 104: 1373-1381, 2009.
256. 2+ channel null mice. EMBO J 22: 3844-3854, 2003.
257. Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klockner U, Wakamori M. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA 90: 6228-6232, 1993.
258. Scott JD, Santana LF. A-kinase anchoring proteins getting to the heart of the matter. Circulation 121: 1264-1271, 2010.
259. Sculptoreanu A, Rotman E, Takahashi M, Scheuer T, Catterall WA. Voltage-dependent potentiation of the activity of cardiac L-type calcium channel-alpha-1 subunits due to phosphorylation by cAMP-dependent protein-kinase. Proc Natl Acad Sci USA 90: 10135-10139, 1993.
260. Seisenberger C, Specht V, Welling A, Platzer J, Pfeifer A, Kuhbandner S, Striessnig J, Klugbauer N, Feil R, Hofmann F. Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse. J Biol Chem 275: 39193-39199, 2000.
261. 2+ channels does not affect their voltage sensor. J Gen Physiol 102: 1005-1030, 1993.
262. Singer-Lahat D, Lotan I, Biel M, Flockerzi V, Hofmann F, Dascal N. Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation. Receptors Channels 2: 215-226, 1994.
263. 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 253: 1553-1557, 1991.
264. 2+ channels. J Clin Invest 113: 1430-1439, 2004.
265. Sklar P, Ripke S, Scott LJ, Andreassen OA, Cichon S, Craddock N, Edenberg HJ, Nurnberger JI, Rietschel M, Blackwood D, Corvin A, Flickinger M, Guan WH, Mattingsdal M, McQuillin A, Kwan P, Wienker TF, Daly M, Dudbridge F, Holmans PA, Lin DY, Burmeister M, Greenwood TA, Hamshere ML, Muglia P, Smith EN, Zandi PP, Nievergelt CM, McKinney R, Shilling PD, Schork NJ, Bloss CS, Foroud T, Koller DL, Gershon ES, Liu CY, Badner JA, Scheftner WA, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon FJ, Schulze TG, Berrettini W, Lohoff FW, Potash JB, Mahon PB, McInnis MG, Zollner S, Zhang P, Craig DW, Szelinger S, Barrett TB, Breuer R, Meier S, Strohmaier J, Witt SH, Tozzi F, Farmer A, McGuffin P, Strauss J, Xu W, Kennedy JL, Vincent JB, Matthews K, Day R, Ferreira MA, O'Dushlaine C, Perlis R, Raychaudhuri S, Ruderfer D, Hyoun PL, Smoller JW, Li J, Absher D, Thompson RC, Meng FG, Schatzberg AF, Bunney WE, Barchas JD, Jones EG, Watson SJ, Myers RM, Akil H, Boehnke M, Chambert K, Moran J, Scolnick E, Djurovic S, Melle I, Morken G, Gill M, Morris D, Quinn E, Muhleisen TW, Degenhardt FA, Mattheisen M, Schumacher J, Maier W, Steffens M, Propping P, Nothen MM, Anjorin A, Bass N, Gurling H, Kandaswamy R, Lawrence J, McGhee K, McIntosh A, McLean AW, Muir WJ, Pickard BS, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Williamson R, Young AH, Ferrier IN, Stefansson K, Stefansson H, Porgeirsson P, Steinberg S, Gustafsson O, Bergen SE, Nimgaonkar V, Hultman C, Landen M, Lichtenstein P, Sullivan P, Schalling M, Osby U, Backlund L, Frisen L, Langstrom N, Jamain S, Leboyer M, Etain B, Bellivier F, Petursson H, Sigurosson E, Muller-Mysok B, Lucae S, Schwarz M, Schofield PR, Martin N, Montgomery GW, Lathrop M, Oskarsson H, Bauer M, Wright A, Mitchell PB, Hautzinger M, Reif A, Kelsoe JR, Purcell SM, DPGCB. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genet 43: 977-U162, 2011.
266. Snutch TP, Leonard JP, Gilbert MM, Lester HA, Davidson N. Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci USA 87: 3391-3395, 1990.
267. Snutch TP, Tomlinson WJ, Leonard JP, Gilbert MM. Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron 7: 45-57, 1991.
268. 2+ channel. Genomics 22: 77-87, 1994.
269. 2+ channel inactivation. Segment exchange analysis of the carboxylterminal cytoplasmic motif encoded by exons 40-42 of the human alpha1C subunit gene. J Biol Chem 273: 957-963, 1998.
270. 2+ dependence of inactivation. J Biol Chem 272: 3560-3566, 1997.
271. 2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325-1358, 2003.
272. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA 102: 8089-8096, 2005.
273. 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 119: 19-31, 2004.
274. Stary A, Shafrir Y, Hering S, Wolschann P, Guy HR. Structural model of the Ca V 1.2 pore. Channels 2: 210-215, 2008.
275. Stotz SC, Jarvis SE, Zamponi GW. Functional roles of cytoplasmic loops and pore lining transmembrane helices in the voltage-dependent inactivation of HVA calcium channels. J Physiol 554: 263-273, 2004.
276. Straub C, Tomita S. The regulation of glutamate receptor trafficking and function by TARPs and other transmembrane auxiliary subunits. Curr Opin Neurobiol 22: 488-495, 2012.
277. 2+ channels. Pflügers Arch 460: 361-374, 2010.
278. 2+ channels with gene knockout models. Channels 2: 233-251, 2008.
279. Strube C. Absence of regulation of the T-type calcium current by Cav1.1, beta1a and gamma1 dihydropyridine receptor subunits in skeletal muscle cells. Pflügers Arch 455: 921-927, 2008.
280. Tadmouri A, Kiyonaka S, Barbado M, Rousset M, Fablet K, Sawamura S, Bahembera E, Pernet-Gallay K, Arnoult C, Miki T, Sadoul K, Gory-Faure S, Lambrecht C, Lesage F, Akiyama S, Khochbin S, Baulande S, Janssens V, Andrieux A, Dolmetsch R, Ronjat M, Mori Y, De Waard M. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. EMBO J 31: 3730-3744, 2012.
281. 2+ channels. Neurosci Res 45: 129-137, 2003.
282. Tanabe T, Adams BA, Numa S, Beam KG. Repeat-I of the dihydropyridine receptor is critical in determining calcium-channel activation kinetics. Nature 352: 800-803, 1991.
283. Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 328: 313-318, 1987.
284. Tang ZZ, Liang MC, Lu S, Yu D, Yu CY, Yue DT, Soong TW. Transcript scanning reveals novel and extensive splice variations in human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit. J Biol Chem 279: 44335-44343, 2004.
285. Tang ZZ, Liao P, Li G, Jiang FL, Yu D, Hong X, Yong TF, Tan G, Lu S, Wang J, Soong TW. Differential splicing patterns of L-type calcium channel Cav1.2 subunit in hearts of Spontaneously Hypertensive Rats and Wistar Kyoto rats. Biochim Biophys Acta 1783: 118-130, 2008.
286. Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL. Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem 286: 10007-10016, 2011.
287. Tang ZZ, Zheng S, Nikolic J, Black DL. Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins. Mol Cell Biol 29: 4757-4765, 2009.
288. Tareilus E, Roux M, Qin N, Olcese R, Zhou JM, 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 USA 94: 1703-1708, 1997.
289. 2+ channels in the rat hippocampus. J Comp Neurol 506: 569-583, 2008.
290. Tiwari S, Zhang Y, Heller J, Abernethy DR, Soldatov NM. Atherosclerosis-related molecular alteration of the human CaV1.2 calcium channel alpha1C subunit. Proc Natl Acad Sci USA 103: 17024-17029, 2006.
291. Tseng GN, Robinson RB, Hoffman BF. Passive properties and membrane currents of canine ventricular myocytes. J Gen Physiol 90: 671-701, 1987.
292. Tsien RW, Lipscombe D, Madison DV, Bley KR, Fox AP. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci 11: 431-438, 1988.
293. 2+ channel-induced calcium release in vascular smooth muscle. Cell Calcium 42: 513-520, 2007.
294. 2+/calmodulin complex. Nat Struct Mol Biol 12: 1108-1115, 2005.
295. 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 429: 671-675, 2004.
296. Waltereit R, Mannhardt S, Nescholta S, Maser-Gluth C, Bartsch D. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response. Learn Mem 15: 348-356, 2008.
297. Wang D, Papp AC, Binkley PF, Johnson JA, Sadee W. Highly variable mRNA expression and splicing of L-type voltage-dependent calcium channel alpha subunit 1C in human heart tissues. Pharmacogenet Genom 16: 735-745, 2006.
298. Wegener JW, Schulla V, Koller A, Klugbauer N, Feil R, Hofmann F. Control of intestinal motility by the Ca(v)1.2 L-type calcium channel in mice. FASEB J 20: 1260-1262, 2006.
299. Wegener JW, Schulla V, Lee TS, Koller A, Feil S, Feil R, Kleppisch T, Klugbauer N, Moosmang S, Welling A, Hofmann F. An essential role of Cav1.2 L-type calcium channel for urinary bladder function. FASEB J 18: 1159-1161, 2004.
300. 2+ channel activity by deletions at the carboxyl terminus of the cardiac alpha 1 subunit. J Biol Chem 269: 1635-1640, 1994.
301. 2+ channel CaV1.2 via the beta-adrenergic-camp-protein kinase A pathway: old dogmas, advances, and new uncertainties. Circ Res 113: 617-631, 2013.
302. 2+/-embryos impairs cardiac development and contraction with secondary defects in vascular maturation. Circ Res 99: 749-757, 2006.
303. Welling A, Bosse E, Cavalie A, Bottlender R, Ludwig A, Nastainczyk W, Flockerzi V, Hofmann F. Stable co-expression of calcium channel alpha 1, beta and alpha 2/delta subunits in a somatic cell line. J Physiol 471: 749-765, 1993.
304. 2+ channels. Circ Res 81: 526-532, 1997.
305. 2+-sensitive ion channels. Cell Calcium 34: 211-229, 2003.
306. 2+ signaling to control CREB-dependent gene expression. Cell 149: 1112-1124, 2012.
307. White JA, McKinney BC, John MC, Powers PA, Kamp TJ, Murphy GG. Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. Learn Mem 15: 1-5, 2008.
308. Williams ME, Marubio LM, Deal CR, Hans M, Brust PF, Philipson LH, Miller RJ, Johnson EC, Harpold MM, Ellis SB. Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. J Biol Chem 269: 22347-22357, 1994.
309. 2+ channel complex purified from brain. Science 261: 486-489, 1993.
310. Wycisk KA, Budde B, Feil S, Skosyrski S, Buzzi F, Neidhardt J, Glaus E, Nurnberg P, Ruether K, Berger W. Structural and functional abnormalities of retinal ribbon synapses due to Cacna2d4 mutation. Invest Ophthalmol Visual Sci 47: 3523-3530, 2006.
311. Wycisk KA, Zeitz C, Feil S, Wittmer M, Forster U, Neidhardt J, Wissinger B, Zrenner E, Wilke R, Kohl S, Berger W. Mutation in the auxiliary calcium-channel subunitCACNA2D4 causes autosomal recessive cone dystrophy. Am J Hum Genet 79: 973-977, 2006.
312. 2+ channel. J Gen Physiol 126: 205-212, 2005.
313. Xu L, Lai D, Cheng J, Lim HJ, Keskanokwong T, Backs J, Olson EN, Wang Y. Alterations of L-type calcium current and cardiac function in CaMKII knockout mice. Circ Res 107: 398-407, 2010.
314. Xu M, Welling A, Paparisto S, Hofmann F, Klugbauer N. Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav12-deficient mice. J Biol Chem 278: 40837-40841, 2003.
315. 2+ channels. Nature 366: 158-161, 1993.
316. Yang L, Katchman A, Morrow JP, Doshi D, Marx SO. Cardiac L-type calcium channel (Cav1.2) associates with gamma subunits. FASEB J 25: 928-936, 2011.
317. 2+ channel does not require phosphorylation of alpha1C Ser1700. Circ Res 113: 871-880, 2013.
318. Yang SN, Berggren PO. The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology. Endocr Rev 27: 621-676, 2006.
319. Yoshida A, Takahashi M, Nishimura S, Takeshima H, Kokubun S. Cyclic AMP-dependent phosphorylation and regulation of the cardiac dihydropyridine-sensitive Ca channel. FEBS Lett 309: 343-349, 1992.
320. Yuan W, Bers DM. Ca-dependent facilitation of cardiac Ca current is due to Cacalmodulin-dependent protein kinase. Am J Physiol Heart Circ Physiol 267: H982-H993, 1994.
321. 2+ channels interacts with and regulates the activity of a novel isoform of Pax6. J Biol Chem 285: 2527-2536, 2010.
322. 2+ channel. J Gen Physiol 126: 193-204, 2005.
323. Zong X, Schreieck J, Mehrke G, Welling A, Schuster A, Bosse E, Flockerzi V, Hofmann F. On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation. Pflügers Arch 430: 340-347, 1995.
324. Zucker RS. Calcium-and activity-dependent synaptic plasticity. Curr Opin Neurobiol 9: 305-313, 1999.
325. Zuhlke RD, Pitt GS, Deisseroth K, Tsien RW, Reuter H. Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature 399: 159-162, 1999.
326. 2+ channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the(alpha)1C subunit. J Biol Chem 275: 21121-21129, 2000.
327. 2+ channels depends on multiple cytoplasmic amino acid sequences of the alpha(1C) subunit. Proc Natl Acad Sci USA 95: 3287-3294, 1998.