Skip to main content
SpringerLink
Log in

Sensory Pathway Modulation by Calcium Channel α2δ1 Subunit

  • Chapter
  • First Online:
Modulation of Presynaptic Calcium Channels

Abstract

Voltage-gated calcium channels (VGCC) are importantly involved in modulation of pathophysiological functions, including the transduction of nociceptive and non-nociceptive signals. As an auxiliary subunit of VGCC, the α2δ (Cavα2δ) subunit plays critical roles in modulating VGCC expression and functions such as regulations of VGCC trafficking, kinetics of voltage-dependent activation and inactivation. Cavα2δ also modulates neuronal and synaptic functions through both VGCC-dependent and independent mechanisms. Among Cavα2δ1–4 subunits, Cavα2δ1 subunit is implicated in pain processing because (1) its upregulation in neuropathic pain models is shown to play a critical role in the onset and maintenance of pain states; (2) its upregulation in sensory neurons leads to dorsal spinal cord neuron sensitization; (3) it is the receptor for gabapentinoids that can normalize activity of sensitized dorsal spinal cord neurons, and have anti-neuropathic pain properties in animal models and patients. In this chapter, we briefly review the regulation of Cavα2δ and its functional contribution to pathophysiological conditions with a main focus on pain transduction and processing. Underlying mechanisms related to Cavα2δ1 contributions to pain processing and the therapeutic effects of gabapentinoids are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arikkath J, Campbell KP (2003) Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr Opin Neurobiol 13:298–307

    Article  PubMed  CAS  Google Scholar 

  • Arikkath J, Chen CC, Ahern C, Allamand V, Flanagan JD, Coronado R, Gregg RG, Campbell KP (2003) Gamma 1 subunit interactions within the skeletal muscle L-type voltage-gated calcium channels. J Biol Chem 278:1212–1219

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Bean BP (1989) Classes of calcium channels in vertebrate cells. Annu Rev Physiol 51:367–384

    Article  PubMed  CAS  Google Scholar 

  • Bee LA, Dickenson AH (2008) Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 140:209–223

    Article  PubMed  CAS  Google Scholar 

  • Bernstein GM, Jones OT (2007) Kinetics of internalization and degradation of N-type voltage-gated calcium channels: role of the alpha2/delta subunit. Cell Calcium 41:27–40

    Article  PubMed  CAS  Google Scholar 

  • Boroujerdi A, Kim HK, Lyu YS, Kim DS, Figueroa KW, Chung JM, Luo ZD (2008) Injury discharges regulate calcium channel a2d1 subunit upregulation in the dorsal horn that contributes to initiation of neuropathic pain. Pain 139:358–366

    Article  PubMed  CAS  Google Scholar 

  • Boroujerdi A, Zeng J, Sharp K, Kim D, Steward O, Luo ZD (2011) Calcium channel a2d1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states. Pain 152:649–655

    Article  PubMed  CAS  Google Scholar 

  • Brickley K, Campbell V, Berrow N, Leach R, Norman RI, Wray D, Dolphin AC, Baldwin SA (1995) Use of site-directed antibodies to probe the topography of the alpha 2 subunit of voltage-gated Ca2+ channels. FEBS Lett 364:129–133

    Article  PubMed  CAS  Google Scholar 

  • Brodbeck J, Davies A, Courtney JM, Meir A, Balaguero N, Canti C, Moss FJ, Page KM, Pratt WS, 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

    Article  PubMed  CAS  Google Scholar 

  • Buraei Z, Yang J (2010) The β subunit of voltage-gated Ca2+ channels. Physiol Rev 90:1461–1506

    Article  PubMed  CAS  Google Scholar 

  • Canti C, Dolphin AC (2003) CaVbeta subunit-mediated up-regulation of CaV2.2 currents triggered by D2 dopamine receptor activation. Neuropharmacology 45:814–827

    Article  PubMed  CAS  Google Scholar 

  • 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 Ca2+ channels. Proc Natl Acad Sci USA 102:11230–11235

    Article  PubMed  CAS  Google Scholar 

  • Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555

    Article  PubMed  CAS  Google Scholar 

  • Chang CY, Chen X, Sandhu A, LI C-Y, Luo ZD (2012) Spinal 5-HT3 receptors facilitate behavioral hypersensitivity induced by elevated calcium channel alpha-2-deltal-1 protein. Eur J of Pain. In press

    Google Scholar 

  • Chaplan SR, Malmberg AB, Yaksh TL (1997) Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J Pharmacol Exp Ther 280:829–838

    PubMed  CAS  Google Scholar 

  • 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 a1-b subunit interaction of voltage-gated Ca2+ channels. Nature 429:675–680

    Article  PubMed  CAS  Google Scholar 

  • Chen RS, Deng TC, Garcia T, Sellers ZM, Best PM (2007) Calcium channel gamma subunits: a functionally diverse protein family. Cell Biochem Biophys 47:178–186

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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 GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci USA 107:1654–1659

    Article  PubMed  CAS  Google Scholar 

  • De Waard M, Witcher DR, Pragnell M, Liu H, Campbell KP (1995) Properties of the alpha 1-beta anchoring site in voltage-dependent Ca2+ channels. J Biol Chem 270:12056–12064

    Article  PubMed  Google Scholar 

  • Dolphin AC (2006) A short history of voltage-gated calcium channels. Br J Pharmacol 147(Suppl 1):S56–S62

    PubMed  CAS  Google Scholar 

  • Dolphin AC (2009) Calcium channel diversity: multiple roles of calcium channel subunits. Curr Opin Neurobiol 19:237–244

    Article  PubMed  CAS  Google Scholar 

  • Dworkin RH, Kirkpatrick P (2005) Pregabalin. Nat Rev Drug Discov 4:455–456

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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 (2000) Nomenclature of voltage-gated calcium channels. Neuron 25:533–535

    Article  PubMed  CAS  Google Scholar 

  • Fedulova SA, Kostyuk PG, Veselovsky NS (1985) Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. J Physiol 359:431–446

    PubMed  CAS  Google Scholar 

  • Felix R (1999) Voltage-dependent Ca2+ channel alpha2delta auxiliary subunit: structure, function and regulation. Recept Channels 6:351–362

    PubMed  CAS  Google Scholar 

  • Felix R, Gurnett CA, De Waard M, Campbell KP (1997) Dissection of functional domains of the voltage-dependent Ca2+ channel alpha2delta subunit. J Neurosci 17:6884–6891

    PubMed  CAS  Google Scholar 

  • 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 USA 103:17537–17542

    Article  PubMed  CAS  Google Scholar 

  • Freise D, Held B, Wissenbach U, Pfeifer A, Trost C, Himmerkus N, Schweig U, Freichel M, Biel M, Hofmann F, Hoth M, Flockerzi V (2000) Absence of the gamma subunit of the skeletal muscle dihydropyridine receptor increases L-type Ca2+ currents and alters channel inactivation properties. J Biol Chem 275:14476–14481

    Article  PubMed  CAS  Google Scholar 

  • Gao B, Sekido Y, Maximov A, Saad M, Forgacs E, Latif F, Wei MH, Lerman M, Lee JH, Perez-Reyes E, Bezprozvanny I, Minna JD (2000) Functional properties of a new voltage-dependent calcium channel alpha2delta auxiliary subunit gene (CACNA2D2). J Biol Chem 275:12237–12242

    Article  PubMed  CAS  Google Scholar 

  • Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN (1996) The novel anticonvulsant drug, gabapentin (neurontin), binds to the a2d subunit of a calcium channel. J Biol Chem 271:5768–5776

    Article  PubMed  CAS  Google Scholar 

  • Gong HC, Hang J, Kohler W, Li L, Su TZ (2001) Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes. J Membr Biol 184:35–43

    Article  PubMed  CAS  Google Scholar 

  • Guay DR (2005) Pregabalin in neuropathic pain: a more “pharmaceutically elegant” gabapentin? Am J Geriatr Pharmacother 3:274–287

    Article  PubMed  CAS  Google Scholar 

  • Gurnett CA, De Waard M, Campbell KP (1996) Dual function of the voltage-dependent Ca2+ channel alpha 2 delta subunit in current stimulation and subunit interaction. Neuron 16:431–440

    Article  PubMed  CAS  Google Scholar 

  • Gurnett CA, Felix R, Campbell KP (1997) Extracellular interaction of the voltage-dependent Ca2+ channel alpha2delta and alpha1 subunits. J Biol Chem 272:18508–18512

    Article  PubMed  CAS  Google Scholar 

  • Hayashida K, DeGoes S, Curry R, Eisenach JC (2007) Gabapentin activates spinal noradrenergic activity in rats and humans and reduces hypersensitivity after surgery. Anesthesiology 106:557–562

    Article  PubMed  CAS  Google Scholar 

  • Hayashida K, Obata H, Nakajima K, Eisenach JC (2008) Gabapentin acts within the locus coeruleus to alleviate neuropathic pain. Anesthesiology 109:1077–1084

    Article  PubMed  CAS  Google Scholar 

  • Heblich F, Tran Van Minh A, Hendrich J, Watschinger K, Dolphin AC (2008) Time course and specificity of the pharmacological disruption of the trafficking of voltage-gated calcium channels by gabapentin. Channels (Austin) 2:4–9

    Article  Google Scholar 

  • Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N (2000) Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neurosci 12:1217–1226

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Lacinova L, Klugbauer N (1999) Voltage-dependent calcium channels: from structure to function. Rev Physiol Biochem Pharmacol 139:33–87

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Hwang JH, Yaksh TL (1997) Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat. Reg Anesth 22:249–256

    Article  PubMed  CAS  Google Scholar 

  • Jay SD, Ellis SB, McCue AF, Williams ME, Vedvick TS, Harpold MM, Campbell KP (1990) Primary structure of the gamma subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 248:490–492

    Article  PubMed  CAS  Google Scholar 

  • Kang MG, Campbell KP (2003) Gamma subunit of voltage-activated calcium channels. J Biol Chem 278:21315–21318

    Article  PubMed  CAS  Google Scholar 

  • Karunasekara Y, Dulhunty AF, Casarotto MG (2009) The voltage-gated calcium-channel beta subunit: more than just an accessory. Eur Biophys J 39:75–81

    Article  PubMed  CAS  Google Scholar 

  • Kim MS, Morii T, Sun LX, Imoto K, Mori Y (1993) Structural determinants of ion selectivity in brain calcium channel. FEBS Lett 318:145–148

    Article  PubMed  CAS  Google Scholar 

  • Kim DS, Figueroa KW, Li KW, Boroujerdi A, Yolo T, Luo ZD (2009) Profiling of dynamically changed gene expression in dorsal root ganglia post peripheral nerve injury and a critical role of injury-induced glial fibrillary acidic protein in maintenance of pain behaviors [corrected]. Pain 143:114–122

    Article  PubMed  CAS  Google Scholar 

  • Kim DS, Li KW, Boroujerdi A, Peter Yu Y, Zhou CY, Deng P, Park J, Zhang X, Lee J, Corpe M, Sharp K, Steward O, Eroglu C, Barres B, Zaucke F, Xu ZC, Luo ZD (2012) Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states. J Neurosci 32:8977–8987

    Article  PubMed  CAS  Google Scholar 

  • Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F (1999) Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci 19:684–691

    PubMed  CAS  Google Scholar 

  • Klugbauer N, Marais E, Hofmann F (2003) Calcium channel alpha2delta subunits: differential expression, function, and drug binding. J Bioenerg Biomembr 35:639–647

    Article  PubMed  CAS  Google Scholar 

  • Kuo CC, Hess P (1993) Ion permeation through the L-type Ca2+ channel in rat phaeochromocytoma cells: two sets of ion binding sites in the pore. J Physiol 466:629–655

    PubMed  CAS  Google Scholar 

  • Kurshan PT, Oztan A, Schwarz TL (2009) Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions. Nat Neurosci 12:1415–1423

    Article  PubMed  CAS  Google Scholar 

  • Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FS 2nd, Mori Y, Campbell KP, Frankel WN (1998) The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat Genet 19:340–347

    Article  PubMed  CAS  Google Scholar 

  • Li CY, Song YH, Higuera ES, Luo ZD (2004) Spinal dorsal horn calcium channel a2d1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci 24:8494–8499

    Article  PubMed  CAS  Google Scholar 

  • Li CY, Zhang XL, Matthews EA, Li KW, Kurwa A, Boroujerdi A, Gross J, Gold MS, Dickenson AH, Feng G, Luo ZD (2006) Calcium channel a2d1 subunit mediates spinal hyperexcitability in pain modulation. Pain 125:20–34

    Article  PubMed  CAS  Google Scholar 

  • Luo ZD (2000) Rat dorsal root ganglia express distinctive forms of the a2 calcium channel subunit. Neuroreport 11:3449–3452

    Article  PubMed  CAS  Google Scholar 

  • Luo ZD (2004) Mechanistic dissection of pain: from DNA to animal models. Methods Mol Med 99:1–10

    PubMed  Google Scholar 

  • Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, Yaksh TL (2001) Upregulation of dorsal root ganglion a2d calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 21:1868–1875

    PubMed  CAS  Google Scholar 

  • Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, Myers RR (2002) Injury type-specific calcium channel a2d1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 303:1199–1205

    Article  PubMed  CAS  Google Scholar 

  • Marais E, Klugbauer N, Hofmann F (2001) Calcium channel alpha2delta subunits-structure and gabapentin binding. Mol Pharmacol 59:1243–1248

    PubMed  CAS  Google Scholar 

  • Mori Y, Friedrich T, Kim MS, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T et al (1991) Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398–402

    Article  PubMed  CAS  Google Scholar 

  • Newton RA, Bingham S, Case PC, Sanger GJ, Lawson SN (2001) Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury. Brain Res Mol Brain Res 95:1–8

    Article  PubMed  CAS  Google Scholar 

  • Nguyen D, Deng P, Matthews EA, Kim DS, Feng G, Dickenson AH, Xu ZC, Luo ZD (2009) Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel a2d1 protein-mediated spinal sensitization and behavioral hypersensitivity. Mol Pain 5:6

    Article  PubMed  Google Scholar 

  • Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316:440–443

    Article  PubMed  CAS  Google Scholar 

  • Obermair GJ, Tuluc P, Flucher BE (2008) Auxiliary Ca2+ channel subunits: lessons learned from muscle. Curr Opin Pharmacol 8:311–318

    Article  PubMed  CAS  Google Scholar 

  • Quintero JE, Dooley DJ, Pomerleau F, Huettl P, Gerhardt GA (2011) Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2+ alpha2delta-1 subunit. J Pharmacol Exp Ther 338:240–245

    Article  PubMed  CAS  Google Scholar 

  • Shistik E, Ivanina T, Puri T, Hosey M, Dascal N (1995) Ca2+ Current enhancement by alpha 2/delta and beta subunits in xenopus oocytes: contribution of changes in channel gating and alpha 1 protein level. J Physiol 489(Pt 1):55–62

    PubMed  CAS  Google Scholar 

  • Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N (1991) The roles of the subunits in the function of the calcium channel. Science 253:1553–1557

    Article  PubMed  CAS  Google Scholar 

  • Striessnig J, Koschak A (2008) Exploring the function and pharmacotherapeutic potential of voltage-gated Ca2+ channels with gene knockout models. Channels (Austin) 2:233–251

    Article  Google Scholar 

  • Takahashi M, Catterall WA (1987) Dihydropyridine-sensitive calcium channels in cardiac and skeletal muscle membranes: studies with antibodies against the alpha subunits. Biochemistry 26:5518–5526

    Article  PubMed  CAS  Google Scholar 

  • Takahashi M, Seagar MJ, Jones JF, Reber BF, Catterall WA (1987) Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci USA 84:5478–5482

    Article  PubMed  CAS  Google Scholar 

  • Takasu K, Ono H, Tanabe M (2008) Gabapentin produces PKA-dependent pre-synaptic inhibition of GABAergic synaptic transmission in LC neurons following partial nerve injury in mice. J Neurochem 105:933–942

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi Y, Takasu K, Ono H, Tanabe M (2007a) Pregabalin, S-(+)-3-isobutylgaba, activates the descending noradrenergic system to alleviate neuropathic pain in the mouse partial sciatic nerve ligation model. Neuropharmacology 53:842–853

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi Y, Takasu K, Honda M, Ono H, Tanabe M (2007b) Neurochemical evidence that supraspinally administered gabapentin activates the descending noradrenergic system after peripheral nerve injury. Eur J Pharmacol 556:69–74

    Article  PubMed  CAS  Google Scholar 

  • Tanabe M, Takasu K, Kasuya N, Shimizu S, Honda M, Ono H (2005) Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. Br J Pharmacol 144:703–714

    Article  PubMed  CAS  Google Scholar 

  • Valder CR, Liu JJ, Song YH, Luo ZD (2003) Coupling gene chip analyses and rat genetic variances in identifying potential target genes that may contribute to neuropathic allodynia development. J Neurochem 87:560–573

    Article  PubMed  CAS  Google Scholar 

  • Whittaker CA, Hynes RO (2002) Distribution and evolution of von Willebrand/integrin a domains: widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell 13:3369–3387

    Article  PubMed  CAS  Google Scholar 

  • Witcher DR, De Waard M, Liu H, Pragnell M, Campbell KP (1995) Association of native Ca2+ channel beta subunits with the alpha 1 subunit interaction domain. J Biol Chem 270:18088–18093

    Article  PubMed  CAS  Google Scholar 

  • Xiao W, Boroujerdi A, Bennett GJ, Luo ZD (2007) Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit. Neuroscience 144:714–720

    Article  PubMed  CAS  Google Scholar 

  • Yusaf SP, Goodman J, Pinnock RD, Dixon AK, Lee K (2001) Expression of voltage-gated calcium channel subunits in rat dorsal root ganglion neurons. Neurosci Lett 311:137–141

    Article  PubMed  CAS  Google Scholar 

  • Zareba G (2005) Pregabalin: a new agent for the treatment of neuropathic pain. Drugs Today (Barc) 41:509–516

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was partially supported by NIH grants (NS064341 and DE021847) to ZD Luo.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of California Irvine, School of Medicine, 837 Health Science Road, Irvine, CA, 92697, USA

    Chunyi Zhou & Z. David Luo

  2. Department of Anesthesiology & Perioperative Care, University of California Irvine, School of Medicine, 837 Health Science Road, Irvine, CA, 92697, USA

    Z. David Luo

Authors
  1. Chunyi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z. David Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z. David Luo .

Editor information

Editors and Affiliations

  1. , School of Pharmacy, University of Reading, Whiteknights, Hopkins Building, Reading, RG6 6UB, Berkshire, United Kingdom

    Gary Stephens

  2. , Department of Physiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Sumiko Mochida

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Zhou, C., Luo, Z.D. (2013). Sensory Pathway Modulation by Calcium Channel α2δ1 Subunit. In: Stephens, G., Mochida, S. (eds) Modulation of Presynaptic Calcium Channels. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6334-0_15

Download citation

Publish with us

Policies and ethics

Search

Navigation