Neuronal functions of auxiliary calcium channel subunits

Modulation of Presynaptic Calcium Channels

Volumn 9789400763340, Issue , 2013, Pages 29-59

  Obermair, Gerald J ^a   Flucher, Bernhard E ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Channel trafficking; High voltage activated Ca2+ channels; Synaptic transmission; Voltage gated calcium channels; 2 ;

Indexed keywords

EID: 84933501797     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-94-007-6334-0_2     Document Type: Chapter

References (146)

1. Alden KJ, Garcia J (2001) Differential effect of gabapentin on neuronal and muscle calcium currents. J Pharmacol Exp Ther 297:727-735
2. Alix JJ, Dolphin AC, Fern R (2008) Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formation. J Physiol 586:4069-4089
3. Altier C, Dubel SJ, Barrere C, Jarvis SE, Stotz SC, Spaetgens RL, Scott JD, Cornet V, DeWaardM, Zamponi GW, Nargeot J, Bourinet E (2002) Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79. J Biol Chem 277:33598-33603
4. Altier C, Garcia-Caballero A, Simms B, You H, Chen L, Walcher J, Tedford HW, Hermosilla T, Zamponi GW (2011) The Cavbeta subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Nat Neurosci 14:173-180
5. Anantharaman V, Aravind L (2000) Cache-a signaling domain common to animal Ca2C-channel subunits and a class of prokaryotic chemotaxis receptors. Trends Biochem Sci 25:535-537
6. Arikkath J, Campbell KP (2003) Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr Opin Neurobiol 13:298-307
7. Ball SL, Powers PA, Shin HS, Morgans CW, Peachey NS, Gregg RG (2002) Role of the beta2 subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest Ophthalmol Vis Sci 43:1595-1603
8. 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 (2001) 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
9. Barnes S, Kelly ME (2002) Calcium channels at the photoreceptor synapse. Adv Exp Med Biol 514:465-476
10. Bauer CS, Nieto-Rostro M, Rahman W, Tran-Van-Minh A, Ferron L, Douglas L, Kadurin I, Sri Ranjan Y, Fernandez-Alacid L, Millar NS, Dickenson AH, Lujan R, Dolphin AC (2009) The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci 29: 4076-4088
11. Beguin P, Mahalakshmi RN, Nagashima K, Cher DH, Ikeda H, Yamada Y, Seino Y, Hunziker W (2006) Nuclear sequestration of beta-subunits by Rad and Rem is controlled by 14-3-3 and calmodulin and reveals a novel mechanism for Ca2C channel regulation. J Mol Biol 355:34-46
12. Berkefeld H, Sailer CA, Bildl W, Rohde V, Thumfart JO, Eble S, Klugbauer N, Reisinger E, Bischofberger J, Oliver D, Knaus HG, Schulte U, Fakler B (2006) BKCa-Cav channel complexes mediate rapid and localized Ca2C-activated KC signaling. Science 314: 615-620
13. Berrow NS, Campbell V, Fitzgerald EM, Brickley K, Dolphin AC (1995) Antisense depletion of beta-subunits modulates the biophysical and pharmacological properties of neuronal calcium channels. J Physiol 482 (Pt 3):481-491
14. Bichet D, Cornet V, Geib S, Carlier E, Volsen S, Hoshi T, Mori Y, De Waard M (2000) The I-II loop of the Ca2C channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 25:177-190
15. Brill J, Klocke R, Paul D, Boison D, Gouder N, Klugbauer N, Hofmann F, Becker CM, Becker K (2004) Entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse. J Biol Chem 279:7322-7330
16. Brodbeck J, Davies A, Courtney JM, Meir A, Balaguero N, Canti C,Moss FJ, Page KM, PrattWS, Hunt SP, Barclay J, Rees M, Dolphin AC (2002) The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function. J Biol Chem 277:7684-7693
17. Bryans JS, Wustrow DJ (1999) 3-substituted GABA analogs with central nervous system activity: a review. Med Res Rev 19:149-177
18. Bucurenciu I, Bischofberger J, Jonas P (2010) A small number of open Ca2C channels trigger transmitter release at a central GABAergic synapse. Nat Neurosci 13:19-21
19. Buraei Z, Yang J (2010) The ss subunit of voltage-gated Ca2C channels. Physiol Rev 90:1461-1506
20. Burgess DL, Jones JM,MeislerMH, Noebels JL (1997)Mutation of the Ca2C channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 88:385-392
21. Calderon-Rivera A, Andrade A, Hernandez-Hernandez O, Gonzalez-Ramirez R, Sandoval A, Rivera M, Gomora JC, Felix R (2012) Identification of a disulfide bridge essential for structure and function of the voltage-gated Ca2C channel alpha2delta-1 auxiliary subunit. Cell Calcium 51:22-30
22. Campiglio M, Di Biase V, Tuluc P, Flucher BE (2013) Stable incorporation vs. dynamic exchange of " subunits in a native calcium channel complex. J Cell Sci [advance online] doi:10.1242/jcs.jcs124537
23. Canti C, Bogdanov Y, Dolphin AC (2000) Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes. J Physiol 527:419-432
24. Canti C, Nieto-Rostro M, Foucault I, Heblich F, Wratten J, Richards MW, Hendrich J, Douglas L, Page KM, Davies A, Dolphin AC (2005) The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2C channels. Proc Natl Acad Sci U S A 102:11230-11235
25. Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947
26. Chen YH, Li MH, Zhang Y, He LL, Yamada Y, Fitzmaurice A, Shen Y, Zhang H, Tong L, Yang J (2004) Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2C channels. Nature 429:675-680
27. Chen H, Puhl HL 3rd, Niu SL, Mitchell DC, Ikeda SR (2005) Expression of Rem2, an RGK family small GTPase, reduces N-type calcium current without affecting channel surface density. J Neurosci 25:9762-9772
28. Chioza BA, Aicardi J, Aschauer H, Brouwer O, Callenbach P, Covanis A, Dooley JM, Dulac O, Durner M, Eeg-Olofsson O, Feucht M, Friis ML, Guerrini R, Kjeldsen MJ, Nabbout R, Nashef L, Sander T, Siren A, Wirrell E, McKeigue P, Robinson R, Gardiner RM, Everett KV (2009) Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14. Epilepsy Res 87:247-255
29. Cole RL, Lechner SM, Williams ME, Prodanovich P, Bleicher L, Varney MA, Gu G (2005) Differential distribution of voltage-gated calcium channel alpha-2 delta (alpha2delta) subunit mRNA-containing cells in the rat central nervous system and the dorsal root ganglia. J Comp Neurol 491:246-269
30. Colecraft HM, Alseikhan B, Takahashi SX, Chaudhuri D, Mittman S, Yegnasubramanian V, Alvania RS, Johns DC, Marban E, Yue DT (2002) Novel functional properties of Ca2C channel beta subunits revealed by their expression in adult rat heart cells. J Physiol 541: 435-452
31. Correll RN, Botzet GJ, Satin J, Andres DA, Finlin BS (2008) Analysis of the Rem2-voltage dependant calcium channel beta subunit interaction and Rem2 interaction with phosphorylated phosphatidylinositide lipids. Cell Signal 20:400-408
32. Dai S, Hall DD, Hell JW (2009) Supramolecular assemblies and localized regulation of voltagegated ion channels. Physiol Rev 89:411-452
33. Davare MA, Avdonin V, Hall DD, Peden EM, Burette A, Weinberg RJ, Horne MC, Hoshi T, Hell JW (2001) A beta2 adrenergic receptor signaling complex assembled with the Ca2C channel Cav1.2. Science 293:98-101
34. Davies A, Douglas L, Hendrich J, Wratten J, Tran Van Minh A, Foucault I, Koch D, Pratt WS, Saibil HR, Dolphin AC (2006) The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function. J Neurosci 26:8748-8757
35. Davies A, Hendrich J, Van Minh AT,Wratten J, Douglas L, Dolphin AC (2007) Functional biology of the alpha2delta subunits of voltage-gated calcium channels. Trends Pharmacol Sci 28: 220-228
36. Davies A, Kadurin I, Alvarez-Laviada A, Douglas L, Nieto-Rostro M, Bauer CS, Pratt WS, Dolphin AC (2010) The alpha2delta subunits of voltage-gated calcium channels form GPIanchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci U S A 107:1654-1659
37. De Waard M, Witcher DR, Pragnell M, Liu H, Campbell KP (1995) Properties of the alpha 1-beta anchoring site in voltage-dependent Ca2C channels. J Biol Chem 270:12056-12064
38. Deisseroth K, Mermelstein PG, Xia H, Tsien RW (2003) Signaling from synapse to nucleus: the logic behind the mechanisms. Curr Opin Neurobiol 13:354-365
39. Dickman DK, Kurshan PT, Schwarz TL (2008) Mutations in a drosophila alpha2delta voltagegated calcium channel subunit reveal a crucial synaptic function. J Neurosci 28:31-38
40. Dolmetsch R (2003) Excitation-transcription coupling: signaling by ion channels to the nucleus. Sci STKE 2003: PE4
41. Dolphin AC (2003) Beta subunits of voltage-gated calcium channels. J Bioenerg Biomembr 35:599-620
42. Dolphin AC (2009) Calcium channel diversity: multiple roles of calcium channel subunits. Curr Opin Neurobiol 19:237-244
43. Dolphin AC (2012) Calcium channel auxiliary alpha2delta and beta subunits: trafficking and one step beyond. Nat Rev Neurosci 13:542-555
44. Donato R, Page KM, Koch D, Nieto-Rostro M, Foucault I, Davies A, Wilkinson T, Rees M, Edwards FA, Dolphin AC (2006) The ducky2J mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression. J Neurosci 26:12576-12586
45. Dooley DJ, Taylor CP, Donevan S, Feltner D (2007) Ca2C channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci 28:75-82
46. Doyle J, Ren X, Lennon G, Stubbs L (1997) Mutations in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice. Mamm Genome 8:113-120
47. Ebert AM,McAnelly CA, Srinivasan A, Linker JL, Horne WA, Garrity DM (2008) Ca2C channelindependent requirement forMAGUK family CACNB4 genes in initiation of zebrafish epiboly. Proc Natl Acad Sci U S A 105:198-203
48. Edvardson S, Oz S, Abulhijaa FA, Taher FB, Shaag A, Zenvirt S, Dascal N, Elpeleg O (2013) Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy. J Med Genet 50:118-123
49. 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 (2009) Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell 139:380-392
50. Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH (2000) Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet 66:1531-1539
51. Fan M, Buraei Z, Luo HR, Levenson-Palmer R, Yang J (2010) Direct inhibition of P/Q-type voltage-gated Ca2C channels by Gem does not require a direct Gem/Cavbeta interaction. Proc Natl Acad Sci U S A 107:14887-14892
52. Fang K, Colecraft HM (2011) Mechanism of auxiliary beta-subunit-mediated membrane targeting of L-type (Ca (V)1.2) channels. J Physiol 589:4437-4455
53. Feng ZP, Arnot MI, Doering CJ, Zamponi GW (2001) Calcium channel beta subunits differentially regulate the inhibition of N-type channels by individual Gbeta isoforms. J Biol Chem 276:45051-45058
54. Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, Bramwell S, Corradini L, England S, Winks J, Kinloch RA, Hendrich J, Dolphin AC, Webb T, Williams D (2006) Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 103: 17537-17542
55. Flucher BE, Phillips JL, Powell JA (1991) Dihydropyridine receptor alpha subunits in normal and dysgenic muscle in vitro: expression of alpha 1 is required for proper targeting and distribution of alpha 2. J Cell Biol 115:1345-1356
56. Fuller MD, Emrick MA, Sadilek M, Scheuer T., Catterall WA (2010) Molecular mechanism of calcium channel regulation in the fight-or-flight response. Sci Signal 3:ra70
57. 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 (2009) Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol 297:H117-H124
58. Gach MP, Cherednichenko G, Haarmann C, Lopez JR, Beam KG, Pessah IN, Franzini-Armstrong C, Allen PD (2008) Alpha2delta1 dihydropyridine receptor subunit is a critical element for excitation-coupled calcium entry but not for formation of tetrads in skeletal myotubes. Biophys J 94:3023-3034
59. Gandini MA, Felix R (2012) Functional interactions between voltage-gated Ca2C channels and Rab3-interacting molecules (RIMs): new insights into stimulus-secretion coupling. Biochim Biophys Acta 1818:551-558
60. Gandini MA, Sandoval A, Gonzalez-Ramirez R, Mori Y, de Waard M, Felix R (2011) Functional coupling of Rab3-interacting molecule 1 (RIM1) and L-type Ca2C channels in insulin release. J Biol Chem 286:15757-15765
61. Gebhart M, Juhasz-Vedres G, Zuccotti A, Brandt N, Engel J, Trockenbacher A, Kaur G, Obermair GJ, Knipper M, Koschak A, Striessnig J (2010) Modulation of Cav1.3 Ca2C channel gating by Rab3 interacting molecule. Mol Cell Neurosci 44:246-259
62. Gregg RG, Messing A, Strube C, Beurg M, Moss R, Behan M, Sukhareva M, Haynes S, Powell JA, Coronado R, Powers PA (1996) Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitationcontraction coupling. Proc Natl Acad Sci U S A 93:13961-13966
63. Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K, Striessnig J, Wratten J, Davies A, Dolphin AC (2008) Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A 105:3628-3633
64. Hendrich J, Bauer CS, Dolphin AC (2012) Chronic pregabalin inhibits synaptic transmission between rat dorsal root ganglion and dorsal horn neurons in culture. Channels 6:124-132
65. Heneghan JF, Mitra-Ganguli T, Stanish LF, Liu L, Zhao R, Rittenhouse AR (2009) The Ca2C channel beta subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current. J Gen Physiol 134:369-384
66. Hernandez-Vivanco A, Perez-Alvarez A, Caba-Gonzalez JC, Alonso MT, Moreno-Ortega AJ, Cano-Abad M, Ruiz-Nuno A, Carmona-Hidalgo B, Albillos A (2012) Selectivity of action of pregabalin on Ca2C channels but not on fusion pore, exocytotic machinery, or mitochondria in chromaffin cells of the adrenal gland. J Pharmacol Exp Ther 342:263-272
67. Hesson LB, Cooper WN, Latif F (2007) Evaluation of the 3p21.3 tumour-suppressor gene cluster. Oncogene 26:7283-7301
68. Hibino H, Pironkova R, Onwumere O, Rousset M, Charnet P, Hudspeth AJ, Lesage F (2003) Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the Ca2C-channel beta 4 subunit. Proc Natl Acad Sci U S A 100:307-312
69. Hoppa MB, Lana B, Margas W, Dolphin AC, Ryan TA (2012) Alpha2delta expression sets presynaptic calcium channel abundance and release probability. Nature 486:122-125
70. Iftinca MC (2011) Neuronal T-type calcium channels: what?s new? Iftinca: T-type channel regulation. J Med Life 4:126-138
71. 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 (2004) Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene. Am J Pathol 165: 1007-1018
72. Jeon D, Song I, Guido W, Kim K, Kim E, Oh U, Shin HS (2008) Ablation of Ca2C channel beta3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory. J Biol Chem 283:12093-12101
73. Johannessen Landmark C (2008) Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 22:27-47
74. Kang MG, Felix R, Campbell KP (2002) Long-term regulation of voltage-gated Ca2C channels by gabapentin. FEBS Lett 528:177-182
75. Kiyonaka S, Wakamori M, Miki T, Uriu Y, Nonaka M, Bito H, Beedle AM, Mori E, Hara Y, De Waard M, Kanagawa M, Itakura M, Takahashi M, Campbell KP, Mori Y (2007) RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2C channels. Nat Neurosci 10:691-701
76. Kurshan PT, Oztan A, Schwarz TL (2009) Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2C-channel functions. Nat Neurosci 12:1415-1423
77. Leyris JP, Gondeau C, Charnet A, Delattre C, Rousset M, Cens T, Charnet P (2009) RGK GTPasedependent CaV2.1 Ca2C channel inhibition is independent of CaVbeta-subunit-induced current potentiation. FASEB J 23:2627-2638
78. Li L, Cao XH, Chen SR, Han HD, Lopez-Berestein G, Sood AK, Pan HL (2012) Up-regulation of Cavbeta3 subunit in primary sensory neurons increases voltage-activated Ca2C channel activity and nociceptive input in neuropathic pain. J Biol Chem 287:6002-6013
79. Liu H, De Waard M, Scott VE, Gurnett CA, Lennon VA, Campbell KP (1996) Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2C channel. J Biol Chem 271:13804-13810
80. Lu SG, Zhang XL, Luo ZD, Gold MS (2010) Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons. Pain 151:633-643
81. Ludwig A, Flockerzi V, Hofmann F (1997) 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
82. Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, Yaksh TL (2001) Upregulation of dorsal root ganglion alpha2delta calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 21:1868-1875
83. Ly CV, Yao CK, Verstreken P, Ohyama T, Bellen HJ (2008) Straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit. J Cell Biol 181:157-170
84. Ma H, Groth RD, Wheeler DG, Barrett CF, Tsien RW (2011) Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation. Neurosci Res 70:2-8
85. Martinez-Hernandez E, Sandoval A, Gonzalez-Ramirez R, Zoidis G, Felix R (2011) Inhibition of recombinant N-type and native high voltage-gated neuronal Ca2C channels by AdGABA: mechanism of action studies. Toxicol Appl Pharmacol 250:270-277
86. Martin-Moutot N, Leveque C, Sato K, Kato R, Takahashi M, Seagar M (1995) Properties of omega conotoxin MVIIC receptors associated with alpha 1A calcium channel subunits in rat brain. FEBS Lett 366:21-25
87. McEnery MW, Snowman AM, Sharp AH, Adams ME, Snyder SH (1991) Purified omegaconotoxin GVIA receptor of rat brain resembles a dihydropyridine-sensitive L-type calcium channel. Proc Natl Acad Sci U S A 88:11095-11099
88. Mercer AJ, ChenM, Thoreson WB (2011) Lateral mobility of presynaptic L-type calcium channels at photoreceptor ribbon synapses. J Neurosci 31:4397-4406
89. Micheva KD, Taylor CP, Smith SJ (2006) Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons. Mol Pharmacol 70:467-476
90. Mochida S, Westenbroek RE, Yokoyama CT, Zhong H, Myers SJ, Scheuer T., Itoh K, Catterall WA (2003) Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels. Proc Natl Acad Sci U S A 100:2819-2824
91. Moosmang S, Haider N, Klugbauer N, Adelsberger H, Langwieser N,Muller J, StiessM,Marais E, Schulla V, Lacinova L, Goebbels S, Nave KA, Storm DR, Hofmann F, Kleppisch T (2005) Role of hippocampal Cav1.2 Ca2C channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci 25:9883-9892
92. Müller CS, Haupt A, Bildl W, Schindler J, Knaus HG, Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B, Schulte U (2010) Quantitative proteomics of the Cav2 channel nanoenvironments in the mammalian brain. Proc Natl Acad Sci U S A 107:14950-14957
93. Murakami M, Nakagawasai O, Yanai K, Nunoki K, Tan-No K, Tadano T, Iijima T (2007) Modified behavioral characteristics following ablation of the voltage-dependent calcium channel beta3 subunit. Brain Res 1160:102-112
94. Namkung Y, Smith SM, Lee SB, Skrypnyk NV, Kim HL, Chin H, Scheller RH, Tsien RW, Shin HS (1998) Targeted disruption of the Ca2C channel beta3 subunit reduces N-and L-type Ca2C channel activity and alters the voltage-dependent activation of P/Q-type Ca2C channels in neurons. Proc Natl Acad Sci U S A 95:12010-12015
95. Neef J, Gehrt A, Bulankina AV, Meyer AC, Riedel D, Gregg RG, Strenzke N, Moser T (2009) The Ca2C channel subunit beta2 regulates Ca2C channel abundance and function in inner hair cells and is required for hearing. J Neurosci 29:10730-10740
96. Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, Griffin RS, Belfer I, Dai F, Smith SB, Diatchenko L, Gupta V, Xia CP, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin SJ, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik JA, Alenius M, Kress M, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ, Penninger JM (2010) A genome-wide Drosophila screen for heat nociception identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell 143:628-638
97. Nimmervoll B, Campiglio M, Lieb A, Schlick B, Di Biase V, Striessnig J, Flucher BE, Obermair GJ (submitted) Auxiliary ?2• subunits of voltage-gated calcium channels differentially regulate synaptic release in hippocampal neurons
98. Obermair GJ, Kugler G, Baumgartner S, Tuluc P, GrabnerM, Flucher BE (2005) The Ca2C channel alpha2delta-1 subunit determines Ca2C current kinetics in skeletal muscle but not targeting of alpha1S or excitation-contraction coupling. J Biol Chem 280:2229-2237
99. Obermair GJ, Tuluc P, Flucher BE (2008) Auxiliary Ca2C channel subunits: lessons learned from muscle. Curr Opin Pharmacol 8:311-318
100. Obermair GJ, Schlick B, Di Biase V, Subramanyam P, Gebhart M, Baumgartner S, Flucher BE (2010) Reciprocal interactions regulate targeting of calcium channel beta subunits and membrane expression of alpha1 subunits in cultured hippocampal neurons. J Biol Chem 285:5776-5791
101. Oliveria SF, Dell?Acqua ML, Sather WA (2007) AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2C channel activity and nuclear signaling. Neuron 55:261-275
102. Opatowsky Y, Chen CC, Campbell KP, Hirsch JA (2004) Structural analysis of the voltagedependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. Neuron 42:387-399
103. Pichler M, Cassidy TN, Reimer D, Haase H, Kraus R, Ostler D, Striessnig J (1997) Beta subunit heterogeneity in neuronal L-type Ca2C channels. J Biol Chem 272:13877-13882
104. Pietrobon D (2010) CaV2.1 channelopathies. Pflug Arch Eur J Phy 460:375-393
105. Pirone A, Rüttiger L, Pilz P, Zuccotti A, Franz C, Friauf E, Knipper M, Engel J (2009) The role of the auxiliary Ca2C channel alpha2delta-3 subunit for signal transmission in the auditory brainstem and the acoustic startle reflex pathway. Program No. 519.8. 2009 Neuroscience Meeting Planner. Society for Neuroscience, Chicago. Online
106. Pravettoni E, Bacci A, Coco S, Forbicini P, Matteoli M, Verderio C (2000) Different localizations and functions of L-type and N-type calcium channels during development of hippocampal neurons. Dev Biol 227:581-594
107. Qin N, Platano D, Olcese R, Costantin JL, Stefani E, Birnbaumer L (1998) Unique regulatory properties of the type 2a Ca2C channel beta subunit caused by palmitoylation. Proc Natl Acad Sci U S A 95:4690-4695
108. Rickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ, Tobias K, Brock JD, Zornberg GL, Pande AC (2005) Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 62:1022-1030
109. Saheki Y, Bargmann CI (2009) Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha (2)delta subunit UNC-36. Nat Neurosci 12:1257-1265
110. Schlick B, Flucher BE, Obermair GJ (2010) Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167:786-798
111. Schredelseker J, Di Biase V, Obermair GJ, Felder ET, Flucher BE, Franzini-Armstrong C, Grabner M (2005) The beta 1a subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle. Proc Natl Acad Sci U S A 102:17219-17224
112. Schweizer FE, Myers KM, Caputo A (2012) In the zone: presynaptic function at high res. Nat Neurosci 15:928-929
113. Scott VE, De Waard M, Liu H, Gurnett CA, Venzke DP, Lennon VA, Campbell KP (1996) Beta subunit heterogeneity in N-type Ca2C channels. J Biol Chem 271:3207-3212
114. Senatore A, Colleoni S, Verderio C, Restelli E, Morini R, Condliffe SB, Bertani I, Mantovani S, Canovi M, Micotti E, Forloni G, Dolphin AC, Matteoli M, Gobbi M, Chiesa R (2012) Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC alpha2delta-1 Subunit. Neuron 74:300-313
115. Sheng ZH, Westenbroek RE, Catterall WA (1998) Physical link and functional coupling of presynaptic calcium channels and the synaptic vesicle docking/fusion machinery. J Bioenerg Biomembr 30:335-345
116. Simms BA, Zamponi GW (2012) Trafficking and stability of voltage-gated calcium channels. Cell Mol Life Sci 69:843-856
117. Sinnegger-Brauns MJ, Huber IG, Koschak A,Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J (2009) Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol 75:407-414
118. 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 (2004) Ca (V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119:19-31
119. Stanley EF (1993) Single calcium channels and acetylcholine release at a presynaptic nerve terminal. Neuron 11:1007-1011
120. Striessnig J (2009) An oily competition: role of beta subunit palmitoylation for Ca2C channel modulation by fatty acids. J Gen Physiol 134:363-367
121. Striessnig J, Bolz HJ, Koschak A (2010) Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltagegated L-type Ca2C channels. Pflug Arch Eur J Phy 460:361-374
122. Subramanyam P, Obermair GJ, Baumgartner S, Gebhart M, Striessnig J, Kaufmann WA, Geley S, Flucher BE (2009) Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells. Channels (Austin) 3:343-355
123. Suh BC, Kim DI, Falkenburger BH, Hille B (2012) Membrane-localized beta-subunits alter the PIP2 regulation of high-voltage activated Ca2C channels. Proc Natl Acad Sci U S A 109: 3161-3166
124. Szabo Z, Obermair GJ, Cooper CB, Zamponi GW, Flucher BE (2006) Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons. Eur J Neurosci 24:709-718
125. 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 (2012) Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. EMBO J 31 (18):3730-3744
126. Takahashi SX,Miriyala J, Tay LH, Yue DT, Colecraft HM (2005) A CaVbeta SH3/guanylate kinase domain interaction regulates multiple properties of voltage-gated Ca2C channels. J Gen Physiol 126:365-377
127. Taylor CP, Garrido R (2008) Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (alpha2-delta) type 1 protein. Neuroscience 155: 510-521
128. Templin C, Ghadri JR, Rougier JS, Baumer A, Kaplan V, Albesa M, Sticht H, Rauch A, Puleo C, Hu D, Barajas-Martinez H, Antzelevitch C, Luscher TF, Abriel H, Duru F (2011) Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 32:1077-1088
129. Tran-Van-Minh A, Dolphin AC (2010) The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2. J Neurosci 30:12856-12867
130. Tuluc P, Kern G, Obermair GJ, Flucher BE (2007) Computer modeling of siRNA knockdown effects indicates an essential role of the Ca2C channel alpha2delta-1 subunit in cardiac excitation-contraction coupling. Proc Natl Acad Sci U S A 104:11091-11096
131. Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr (2004) Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature 429:671-675
132. Van Petegem F, Duderstadt KE, Clark KA, Wang M, Minor DL Jr (2008) Alanine-scanning mutagenesis defines a conserved energetic hotspot in the CaValpha1 AID-CaVbeta interaction site that is critical for channel modulation. Structure 16:280-294
133. Vance CL, Begg CM, Lee WL, Haase H, Copeland TD, McEnery MW (1998) Differential expression and association of calcium channel alpha1B and beta subunits during rat brain ontogeny. J Biol Chem 273:14495-14502
134. Vendel AC, Terry MD, Striegel AR, Iverson NM, Leuranguer V, Rithner CD, Lyons BA, Pickard GE, Tobet SA, Horne WA (2006) Alternative splicing of the voltage-gated Ca2C channel beta4 subunit creates a uniquely folded N-terminal protein binding domain with cell-specific expression in the cerebellar cortex. J Neurosci 26:2635-2644
135. Waithe D, Ferron L, Page KM, Chaggar K, Dolphin AC (2011) beta-subunits promote the expression of CaV2.2 channels by reducing their proteasomal degradation. J Biol Chem 286:9598-9611
136. Weissgerber P, Held B, Bloch W, Kaestner L, Chien KR, Fleischmann BK, Lipp P, Flockerzi V, Freichel M (2006) Reduced cardiac L-type Ca2C current in CaVbeta2-/-embryos impairs cardiac development and contraction with secondary defects in vascular maturation. Circ Res 99:749-757
137. Whittaker CA, Hynes RO (2002) Distribution and evolution of vonWillebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell 13: 3369-3387
138. Witcher DR, DeWaard M, Kahl SD, Campbell KP (1994) Purification and reconstitution of N-type calcium channel complex from rabbit brain. Methods Enzymol 238:335-348
139. Wu ZZ, Li DP, Chen SR, Pan HL (2009) Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit. J Biol Chem 284:36453-36461
140. Wycisk KA, Budde B, Feil S, Skosyrski S, Buzzi F, Neidhardt J, Glaus E, Nurnberg P, Ruether K, Berger W (2006a) Structural and functional abnormalities of retinal ribbon synapses due to Cacna2d4 mutation. Invest Ophthalmol Vis Sci 47:3523-3530
141. Wycisk KA, Zeitz C, Feil S, Wittmer M, Forster U, Neidhardt J, Wissinger B, Zrenner E, Wilke R, Kohl S, Berger W (2006b) Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy. Am J Hum Genet 79:973-977
142. Xie M, Li X, Han J, Vogt DL, Wittemann S, Mark MD, Herlitze S (2007) Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca2C channel Cavbeta4 versus Cavbeta2 subunits to synaptic terminals. J Cell Biol 178:489-502
143. Yang T, Suhail Y, Dalton S, Kernan T, Colecraft HM (2007) Genetically encoded molecules for inducibly inactivating CaV channels. Nat Chem Biol 3:795-804
144. Zamponi GW (2003) Regulation of presynaptic calcium channels by synaptic proteins. J Pharmacol Sci 92:79-83
145. Zhang Y, Yamada Y, Fan M, Bangaru SD, Lin B, Yang J (2010) The beta subunit of voltage-gated Ca2C channels interacts with and regulates the activity of a novel isoform of Pax6. J Biol Chem 285:2527-2536
146. Zheng JQ, Poo MM (2007) Calcium signaling in neuronal motility. Annu Rev Cell Dev Biol 23:375-404