Voltage-Sensitive Calcium Channels in the Brain: Relevance to Alcohol Intoxication and Withdrawal

  • Prosper N’GouemoEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 248)


Voltage-sensitive Ca2+ (CaV) channels are the primary route of depolarization-induced Ca2+ entry in neurons and other excitable cells, leading to an increase in intracellular Ca2+ concentration ([Ca2+]i). The resulting increase in [Ca2+]i activates a wide range of Ca2+-dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca2+-dependent enzymes, and activation of certain K+ channels and chloride channels. In addition to their key roles under physiological conditions, CaV channels are also an important target of alcohol, and alcohol-induced changes in Ca2+ signaling can disturb neuronal homeostasis, Ca2+-mediated gene transcription, and the function of neuronal circuits, leading to various neurological and/or neuropsychiatric symptoms and disorders, including alcohol withdrawal induced–seizures and alcoholism.


Alcohol exposure Alcohol intoxication Alcohol withdrawal seizures Calcium signaling 


  1. Akinfiresoye LR, Miranda C, Lovinger DM, N’Gouemo P (2016) Alcohol withdrawal increases protein kinase A activity in the rat inferior colliculus. Alcohol Clin Exp 40:2359–2367Google Scholar
  2. Albowitz B, König P, Kuhnt U (1997) Spatiotemporal distribution of intracellular calcium transients during epileptiform activity in guinea pig hippocampal slices. J Neurophysiol 77:491–501PubMedGoogle Scholar
  3. Anderson D, Rehak R, Hameed S, Mehaffey WH, Zamponi GW, Turner RW (2010) Regulation of the KV4.2 complex by CaV3.1 calcium channels. Channels (Austin) 4:163–167Google Scholar
  4. Berkefeld H, Fakler B, Schulte U (2010) Ca2+-activated K+ channels: from protein complexes to function. Physiol Rev 90:1437–1459PubMedGoogle Scholar
  5. Berridge MJ (2012) Calcium signalling remodelling and disease. Biochem Soc Trans 40:297–309PubMedGoogle Scholar
  6. Bouchenafa O, Littleton JM (1998) Expression of c-Fos protein immunoreactivity in rat brain during ethanol withdrawal is prevented by nifedipine. Alcohol 15:71–77PubMedGoogle Scholar
  7. Brennan CH, Crabbe J, Littleton JM (1990) Genetic regulation of dihydropyridine-sensitive calcium channels in brain may determine suscpetibility to physical dependence on alcohol. Neuropharmacology 29:429–432PubMedGoogle Scholar
  8. Cain SM, Snutch TP (2010) Contributions of T-type calcium channel isoforms to neuronal firing. Channels 4:44–51Google Scholar
  9. Cain SM, Snutch TP (2012) Voltage-gated calcium channels in epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper’s basic mechanisms of the epilepsies, 4th edn. Oxford University Press, Bethesda, pp 66–84Google Scholar
  10. Canda A, Yu BH, Sze PY (1995) Biochemical characterization of ethanol actions on dihydropyridine-sensitive calcium channels in brain synaptosomes. Biochem Pharmacol 50:1711–1718PubMedGoogle Scholar
  11. Carden WB, Alexander GM, Friedman DP, Daunais JB, Grant KA, Mu J, Godwin DW (2006) Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates. Brain Res 1089:92–100PubMedGoogle Scholar
  12. Contreras D (2006) The role of T-channels in the generation of thalamocortical rhythms. CNS Neurol Disord Drug Targets 5:571–585PubMedGoogle Scholar
  13. Craig PJ, Beattie RE, Folly EA, Banerjee MD, Reeves MB, Priestley JV, Carney SL, Sher E, Perez-Reyes E, Volsen SG (1999) Distribution of the voltage-dependent calcium channel alpha1G subunit mRNA and protein throughout the mature rat brain. Eur J Neurosci 11:2949–2964PubMedGoogle Scholar
  14. Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E (1998) Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res 83:103–109PubMedGoogle Scholar
  15. Davare MA, Hell JW (2003) Increased phosphorylation of neuronal L-type Ca2+ channel CaV1.2 during aging. Proc Natl Acad Sci U S A 100:16018–16023PubMedPubMedCentralGoogle Scholar
  16. Day NC, Shaw PJ, McCormack AL, Craig PJ, Smith W, Beattie R, Williams TL, Ellis SB, Ince PG, Harpold MM, Lodge D, Volsen SG (1996) Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus. Neuroscience 71:1013–1024PubMedGoogle Scholar
  17. De Beun R, Schneider R, Klein A, Lohmann A, De Vry J (1996a) Effects of nimodipine and other calcium channel antagonists in alcohol-preferring AA rats. Alcohol 13:263–171PubMedGoogle Scholar
  18. De Beun R, Schneider R, Klein A, Lohmann A, Schreiber R, De Vry J (1996b) The calcium channel agonist BAY k 8644 reduces ethanol intake and preference in alcohol-preferring AA rats. Psychopharmacology 127:302–310PubMedGoogle Scholar
  19. Delorenzo RJ, Sun DA, Deshpande LS (2005) Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy. Pharmacol Ther 105:229–266PubMedGoogle Scholar
  20. Diversé-Pierluissi M, Dunlap K (1993) Distinct, convergent second messenger pathways modulate neuronal calcium currents. Neuron 10:753–760PubMedGoogle Scholar
  21. Dolin S, Little H, Hudspith M, Pagonis C, Littleton J (1987) Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology 26:275–279PubMedGoogle Scholar
  22. Dreyfus FM, Tscherter A, Errington AC, Renger JJ, Shin HS, Uebele VN, Crunelli V, Lambert RC, Leresche N (2010) Selective T-type calcium channel block in thalamic neurons reveals channel redundancy and physiological impact of I(T)window. J Neurosci 30:99–109PubMedPubMedCentralGoogle Scholar
  23. Ermolyuk YS, Alder FG, Surges R, Pavlov IY, Timofeeva Y, Kullmann DM, Volynski KE (2013) Differential triggering of spontaneous glutamate release by P/Q-, N-, and R-type Ca2+ channels. Nat Neurosci 16:1754–1763PubMedPubMedCentralGoogle Scholar
  24. Ertel EA, Campbell KP, Harpold MM, Hofmann F, Mori Y, Perez-Reyes E, Schwartz A, Snutch TP, Tanabe Y, Birnbauner L, Tsien RW, Catterall WA (2000) Nomenclature of voltage-gated calcium channels. Neuron 25:533–535PubMedGoogle Scholar
  25. Faber ES, Sah P (2003) Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist 9:181–194PubMedGoogle Scholar
  26. Faingold CL (2008) The Majchrowicz binge alcohol protocol: an intubation technique to study alcohol dependence in rats. Curr Protoc Neurosci. Chapter 9: Unit 9.28Google Scholar
  27. Faingold CL, N’Gouemo P, Riaz A (1998) Ethanol and neurotransmitter interaction-from molecular to integrative effects. Prog Neurobiol 55:509–535PubMedGoogle Scholar
  28. Fournier F, Bourinet E, Nargeot J, Charnet P (1993) Cyclic AMP-dependent regulation of P-type calcium channels expressed in Xenopus oocytes. Pflugers Arch 423:173–180PubMedGoogle Scholar
  29. Gerstin EH, McMahon T, Dadgar J, Messing RO (1998) Protein kinase Cδ mediates ethanol-induced upregulation of L-type calcium channels. J Biol Chem 273:16409–16414PubMedGoogle Scholar
  30. Graef JD, Huitt TW, Nordskog BK, Hammarback JH, Godwin DW (2011) Disrupted thalamic T-type Ca2 channel expression and function during ethanol exposure and withdrawal. J Neurophysiol 105:528–540PubMedGoogle Scholar
  31. Gray R, Johnston D (1987) Noradrenaline and beta-adrenoceptor agonists increase activity of voltage-dependent calcium channels in hippocampal neurons. Nature 327:620–622PubMedGoogle Scholar
  32. Gruol DL, Parsons KL (1994) Chronic exposure to alcohol during development alters the calcium currents of cultured cerebellar Purkinje neurons. Brain Res 624:283–290Google Scholar
  33. Gruol DL, Parsons KL, DiJulio N (1997) Acute ethanol alters calcium signals elicited by glutamate receptor agonists and K+ depolarization in cultured cerebellar Purkinje neurons. Brain Res 773:82–89PubMedGoogle Scholar
  34. Guppy LJ, Crabbe JC, Littleton JM (1995) Time course and genetic variation in the regulation of calcium channel antagonist binding sites in rodent tissues during the induction of ethanol physical dependence and withdrawal. Alcohol Alcohol 30:607–615PubMedGoogle Scholar
  35. Hall AC, Lieb WR, Franks NP (1994) Insensitivity of P-type calcium channels to inhalation and intravenous general anesthetics. Anesthesiology 81:117–123PubMedGoogle Scholar
  36. Heinemann U, Lux HD, Gutnick MJ (1977) Extracellular free calcium and potassium during paroxysmal activity in the cerebral cortex of the cat. Exp Brain Res 27:237–243PubMedGoogle Scholar
  37. Hell JW, Westenbroek RE, Warner C, Ahlijanian MK, Prystay W, Gilbert MM, Snutch TP, Catterall WA (1993) Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J Cell Biol 123:949–962PubMedGoogle Scholar
  38. Hillman D, Chen S, Aung TT, Cherksey B, Sugimori M, Llinas RR (1991) Localization of P-type calcium channels in the central nervous system. Proc Natl Acad Sci U S A 88:7076–7080PubMedPubMedCentralGoogle Scholar
  39. Huang G-J, McArdle JJ (1993) Chronic ingestion of ethanol increases the number of Ca2+ channels of hippocampal neurons of long-sleep but not short-sleep mice. Brain Res 615:328–330PubMedGoogle Scholar
  40. Jahnsen H, Llinas R (1984) Voltage-dependent burst-to-tonic switching of thalamic cell activity: an in vitro study. Arch Ital Biol 122:73–82PubMedGoogle Scholar
  41. Joksovic PM, Brimelow BC, Murbartián J, Perez-Reyes E, Todorovic SM (2005) Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels. Br J Pharmacol 144:59–70PubMedGoogle Scholar
  42. Kanyshkova T, Ehling P, Cerina M, Meuth P, Zobeiri M, Meuth SG, Pape HC, Budde T (2014) Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats. Mol Cell Neurosci 61:110–122PubMedGoogle Scholar
  43. Katsura M, Torigoe F, Hayashida S, Honda T, Tsujimura A, Ohkuma S (2005) Ethanol physical dependence is accompanied by up-regulated expression of L-type high voltage-gated calcium channel alpha1 subunits in mouse brain. Brain Res 1039:211–215PubMedGoogle Scholar
  44. Klöckner U, Lee JH, Cribbs LL, Daud A, Hescheler J, Pereverzev A, Perez-Reyes E, Schneider T (1999) Comparison of the Ca2+ currents induced by expression of three cloned alpha1 subunits, alpha1G, alpha1H and alpha1I, of low-voltage-activated T-type Ca2+ channels. Eur J Neurosci 11:4171–4178PubMedGoogle Scholar
  45. Koschak A, Reimer D, Huber I, Grabner M, Glossmann H, Engel J, Striessnig J (2001) Alpha 1D (Cav1.3) subunits can form L-type Ca2+ channels activating at negative voltages. J Biol Chem 276:22100–22106PubMedGoogle Scholar
  46. Kovács K, Sík A, Ricketts C, Timofeev I (2010) Subcellular distribution of low-voltage activated T-type Ca2+ channel subunits (Ca(v)3.1 and Ca(v)3.3) in reticular thalamic neurons of the cat. J Neurosci 88:448–460Google Scholar
  47. Lee JH, Daud AN, Cribbs LL, Lacerda AE, Pereverzev A, Klöckner U, Schneider T, Perez-Reyes E (1999) Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. J Neurosci 19:1912–1921PubMedGoogle Scholar
  48. Lee Y, Han J-H, Lim C-S, Chang D-J, Lee Y-S, Soh H, Park CS, Kaang BK (2003) Impairment of a parabolic bursting rhythm by the ectopic expression of a small conductance Ca2+-activated K+ channel in Aplysia neuron R15. Neurosci Lett 349:53–57PubMedGoogle Scholar
  49. Little HJ, Dolin SJ, Halsey MJ (1986) Calcium channel antagonists decrease the ethanol withdrawal syndrome. Life Sci 39:2059–2065PubMedGoogle Scholar
  50. Liu XB, Murray KD, Jones EG (2011) Low-threshold calcium channel subunit Cav3.3 is specifically localized in GABAergic neurons of rodent thalamus and cerebral cortex. J Comp Neurol 519:1181–1195PubMedGoogle Scholar
  51. Loane DJ, Lima PA, Marrion NV (2007) Co-assembly of N-type Ca2+ and BK channels underlies functional coupling in rat brain. J Cell Sci 120:985–995PubMedGoogle Scholar
  52. 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 17:1339–1349PubMedGoogle Scholar
  53. Mah SJ, Fleck MW, Lindsley TA (2011) Ethanol alters calcium signaling in axonal growth cones. Neuroscience 189:384–396PubMedPubMedCentralGoogle Scholar
  54. McKay BE, McRory JE, Molineux ML, Hamid J, Snutch TP, Zamponi GW, Turner RW (2006) CaV3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur J Neurosci 24:2581–2594PubMedGoogle Scholar
  55. McMahon T, Andersen R, Metten P, Crabbe JC, Messing RO (2000) Protein kinase C epsilon mediates up-regulation of N-type calcium channels by ethanol. Mol Pharmacol 57:53–58PubMedGoogle Scholar
  56. Mogul DJ, Adams ME, Fox AP (1993) Differential activation of adenosine receptors decreases N-type currents an potentiates P-type Ca2+ currents in hippocampal CA3 neurons. Neuron 10:327–334PubMedGoogle Scholar
  57. Mori Y, Friedrich T, Kim MS, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T, Mikoshiba K, Imoto K, Tanabe T, Numa S (1991) Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398–402PubMedGoogle Scholar
  58. Morton RA, Valenzuela CF (2016) Further characterization of the effect of ethanol on voltage-gated Ca2+ channel function in developing CA3 hippocampal pyramidal neurons. Brain Res 1633:19–26PubMedGoogle Scholar
  59. Mu J, Carden WB, Kurukulasuriya NC, Alexander GM, Godwin DW (2003) Ethanol influences on native T-type calcium current in thalamic sleep circuitry. J Pharmacol Exp Ther 307:197–204PubMedGoogle Scholar
  60. Mulholland PJ, Spencer KB, Hu W, Kroener S, Chandler LJ (2015) Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus. Psychopharmacology 232:1995–2006PubMedGoogle Scholar
  61. N’Gouemo P (2015) Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures. Eur Neuropsychopharmacol 25:1342–1352PubMedPubMedCentralGoogle Scholar
  62. N’Gouemo P, Morad M (2003) Ethanol withdrawal seizure susceptibility is associated with upregulation of L- and P-type Ca2+ channels currents in rat inferior colliculus neurons. Neuropharmacology 45:429–437PubMedGoogle Scholar
  63. N’Gouemo P, Morad M (2014) Alcohol withdrawal is associated with a downregulation of large-conductance Ca2+-activated K+ channels in rat inferior colliculus neurons. Psychopharmacology 231:2009–2018PubMedGoogle Scholar
  64. N’Gouemo P, Yasuda RP, Morad M (2006) Ethanol withdrawal is accompanied by downregulation of calcium channel alpha 1B subunit in rat inferior colliculus neurons. Brain Res 1108:216–220PubMedGoogle Scholar
  65. N’Gouemo P, Akinfiresoye LR, Allard JS, Lovinger DM (2015) Alcohol withdrawal-induced seizure susceptibility is associated with an upregulation of CaV1.3 channels in the rat inferior colliculus. Int J Neuropsychopharmacol 18:pyu123. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Nagao NI, Adachi-Akahane S (2001) Ser1901 of alpha(1c) subunit is required for PKA mediated enhancement of L-type Ca2+ channels currents but not for the negative shift of activation. FEBS Lett 489:87–91PubMedGoogle Scholar
  67. Newton J, N’Gouemo P (2017) Withdrawal seizures. In: Pitkänen A, Buckmaster P, Galanopoulou AS, Moshé SL (eds) Models of seizures and epilepsy, 2nd edn. Academic, San Diego, pp 911–931Google Scholar
  68. Newton PM, Orr CJ, Wallace MJ, Kim C, Shin HS, Messing RO (2004) Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci 24:9862–9869PubMedGoogle Scholar
  69. Newton J, Suman S, Akinfiresoye LR, Datta K, Lovinger DM, N’Gouemo P (2018) Alcohol withdrawal upregulates mRNA encoding for CaV2.1-α1 subunit in the rat inferior colliculus. Alcohol 66:21–16PubMedGoogle Scholar
  70. Oakes SG, Pozos RS (1982a) Electrophysiologic effects of acute ethanol exposure. I. Alterations in the action potentials of dorsal root ganglia neurons in dissociated culture. Brain Res 281:243–249PubMedGoogle Scholar
  71. Oakes SG, Pozos RS (1982b) Electrophysiologic effects of acute ethanol exposure. II. Alterations in the calcium component of action potentials from sensory neurons in dissociated culture. Brain Res 281:251–255PubMedGoogle Scholar
  72. Olson PA, Tkatch T, Hernandez-Lopez S, Ulrich S, Ilijic E, Mugnaini E, Zhang H, Bezprozvanny I, Surmeier DJ (2005) G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J Neurosci 25:1050–1062PubMedGoogle Scholar
  73. Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP, Fox M, Rees M, Lee JH (1998) Molecular characterization of a neuronal low-voltage-activated T-type calcium channel. Nature 391:896–900PubMedGoogle Scholar
  74. Perez-Velazquez JL, Valiante TA, Carlen PL (1994) Changes in calcium currents during ethanol withdrawal in a genetic mouse model. Brain Res 649:305–309PubMedGoogle Scholar
  75. Randall A, Tsien RW (1995) Pharmacological dissection of multiple type of Ca2+ channels in rat cerebellar granule neurons. J Neurosci 15:2995–3012PubMedGoogle Scholar
  76. Rane SG, Dunlap K (1986) Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons. Proc Natl Acad Sci U S A 83:184–188PubMedPubMedCentralGoogle Scholar
  77. Rane SG, Walsh MP, McDonald JR, Dunlap K (1989) Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current. Neuron 3:239–245PubMedGoogle Scholar
  78. Rehak R, Bartoletti TM, Engbers JD, Berecki G, Turner RW, Zamponi GW (2013) Low voltage activation of KCa1.1 current by Cav3-KCa1.1 complexes. PLoS One 8:e61844PubMedPubMedCentralGoogle Scholar
  79. Rezvani AH, Janowsky DS (1990) Decreased alcohol consumption by verapamil in alcohol preferring rats. Prog Neuro-Psychopharmacol Biol Psychiatry 14:623–631Google Scholar
  80. Rezvani AH, Grady DR, Janowsky DS (1991) Effect of calcium-channel blockers on alcohol consumption in alcohol-drinking monkeys. Alcohol Alcohol 26:161–167PubMedGoogle Scholar
  81. Richards KS, Swensen AM, Lipscombe D, Bommert K (2007) Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current. Eur J Neurosci 26:2950–2961PubMedGoogle Scholar
  82. Riegle MA, Masicampo ML, Shan HQ, Xu V, Godwin DW (2015) Ethosuximide reduces mortality and seizure severity in response to pentylenetetrazole treatment during ethanol withdrawal. Alcohol Alcohol 50:501–508PubMedPubMedCentralGoogle Scholar
  83. Riplet TL, Whittington MA, Butterworth AR, Little HJ (1996) Ethanol withdrawal hyperexcitability in vivo and in isolated mouse hippocampal slices. Alcohol Alcohol 31:347–357Google Scholar
  84. Ruhe CA, Littleton JM (1994) The possible role of voltage-operated calcium channels in the enhancement of excitatory amino acid toxicity following chronic ethanol exposure in vitro. Alcohol Alcohol Suppl 2:217–221PubMedGoogle Scholar
  85. Schlick B, Flucher BE, Obermair GJ (2010) Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167:786–798PubMedPubMedCentralGoogle Scholar
  86. Sculptoreanu A, Scheuer T, Catterall WA (1993) Voltage-dependent potentiation of L-type Ca2+ channels due to phosphorylation by cAMP-dependent protein kinase. Nature 364:240–243PubMedGoogle Scholar
  87. Shan HQ, Hammarback JA, Godwin DW (2013) Ethanol inhibition of a T-type Ca2+ channel through activity of protein kinase C. Alcohol Clin Exp Res 37:1333–1342PubMedPubMedCentralGoogle Scholar
  88. Simms BA, Zamponi GW (2014) Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron 82:24–45PubMedGoogle Scholar
  89. 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 75:407–414PubMedGoogle Scholar
  90. Soong TW, Stea A, Hodson CD, Dubel SJ, Vincent SR, Snutch TP (1993) Structure and functional expression of a member of the low voltage-activated calcium channel family. Science 260:1133–1136PubMedGoogle Scholar
  91. Stea A, Soong TW, Snutch TP (1995) Determinants of PKC-dependent modulation of a family of neuronal calcium channels. Neuron 15:929–940PubMedGoogle Scholar
  92. Swayne LA, Bourinet E (2008) Voltage-gated calcium channels in chronic pain: emerging role of alternative splicing. Pflugers Arch 456:459–466PubMedGoogle Scholar
  93. Takao T, Murakami H, Fukuda M, Kawaguchi T, Kakita A, Takahashi H, Kudoh M, Tanaka R, Shibuki K (2006) Transcranial imaging of audiogenic epileptic foci in the cortex of DBA/2J mice. Neuroreport 17:267–271PubMedGoogle Scholar
  94. Talley EM, Cribbs LL, Lee JH, Daud A, Perez-Reyes E, Bayliss DA (1999) Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J Neurosci 19:1895–1911PubMedGoogle Scholar
  95. Thiagarajan TC, Lindskog M, Tsien RW (2005) Adaptation to synaptic inactivity in the hippocampal neurons. Neuron 47:725–737PubMedGoogle Scholar
  96. Tippens AL, Pare JF, Langwieser N, Moosmang S, Milner TA, Smith Y, Lee A (2008) Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type Ca2+ channels in the rat hippocampus. J Comp Neurol 506:569–583PubMedGoogle Scholar
  97. Turner RW, Zamponi GW (2014) T-type channels buddy up. Pflugers Arch 466:661–675PubMedPubMedCentralGoogle Scholar
  98. Varodayan FP, Logrip ML, Roberto M (2017a) P/Q-type voltage-gated calcium channels mediate the ethanol and CRF sensitivity of central amygdala GABAergic synapses. Neuropharmacology 125:197–206PubMedPubMedCentralGoogle Scholar
  99. Varodayan FP, de Guglielmo G, Logrip ML, George O, Roberto M (2017b) Alcohol dependence disrupts amygdalar L-type voltage-gated calcium channel mechanisms. J Neurosci 37:4593–4603PubMedPubMedCentralGoogle Scholar
  100. Volsen SG, Day NC, McCormack AL, Smith W, Craig PJ, Beattie R, Ince PG, Shaw PJ, Ellis SB, Gillespie A, Harpold MM, Lodge D (1995) The expression of neuronal voltage-dependent calcium channels in human cerebellum. Mol Brain Res 34:271–282PubMedGoogle Scholar
  101. Wang X, Dayanithi G, Lemos JR, Nordmann JJ, Treistman SN (1991) Ca2+ currents and peptide release from neurohypophysial terminals are inhibited by ethanol. J Pharmacol Exp Ther 259:705–711PubMedGoogle Scholar
  102. Wang X, Wang G, Lemos JR, Treistman SN (1994) Ethanol directly modulates gating of a dihydropyridine-sensitive Ca2+ channels in neurohypophysial terminals. J Neurosci 14:5453–5460PubMedGoogle Scholar
  103. Watson WP, Little HJ (1999) Correlation between increases in dihydropyridine binding in vivo and behavioural signs of ethanol withdrawal in mice. Alcohol Alcohol 34:35–42PubMedGoogle Scholar
  104. Welsh JP, Han VZ, Rossi DJ, Mohr C, Odagiri M, Daunais JB, Grant KA (2011) Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence. Proc Natl Acad Sci U S A 108:10314–10319PubMedPubMedCentralGoogle Scholar
  105. Westenbroek RE, Ahlijanian MK, Catterall WA (1990) Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons. Nature 347:281–284PubMedGoogle Scholar
  106. Westenbroek RE, Hell JW, Warner C, Dubel SJ, Snutch TP, Catterall WA (1992) Biochemical properties and distribution of N-type calcium channel α1 subunit. Neuron 9:1099–1115PubMedGoogle Scholar
  107. Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TVB, Snutch TP, Catterall WA (1995) Immunochemical identification and subcellular distribution of the α1A subunits of brain calcium channels. J Neurosci 15:6403–6418PubMedGoogle Scholar
  108. Whittington MA, Little HJ (1991) Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal. Br J Pharmacol 103:1677–1684PubMedPubMedCentralGoogle Scholar
  109. Whittington MA, Little HJ (1993) Changes in voltage-operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices. Exp Physiol 78:347–370PubMedGoogle Scholar
  110. Whittington MA, Butterworth AR, Dolin SJ, Patch TL, Little HJ (1992) The effects of chronic treatment with dihydropyridine, Bay K 8644, on hyperexcitability due to ethnaol withdrawal, in vivo and in vitro. Br J Pharmacol 105:285–292PubMedPubMedCentralGoogle Scholar
  111. Whittington MA, Lambert JD, Little HJ (1995) Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability. Alcohol Alcohol 30:105–114PubMedGoogle Scholar
  112. Widmer H, Lemos JR, Treistman SN (1998) Ethanol reduces the duration of single evoked spikes by a selective inhibition of voltage-gated calcium currents in acutely dissociated supraoptic neurons of the rat. J Neuroendocrinol 10:399–406PubMedGoogle Scholar
  113. Xu J, Clancy CE (2008) Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: a model study. PLoS One 3:e2056PubMedPubMedCentralGoogle Scholar
  114. Xu W, Lipscombe D (2001) Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci 21:5944–5951PubMedGoogle Scholar
  115. Xu JH, Long L, Wang J, Tang YC, Hu HT, Soong TW, Tang FR (2010) Nuclear localization of Ca(v)2.2 and its distribution in the mouse central nervous system, and changes in the hippocampus during and after pilocarpine-induced status epilepticus. Neuropathol Appl Neurobiol 36:71–85PubMedGoogle Scholar
  116. Yazdi HH, Janahmadi M, Behzadi G (2007) The role of small-conductance Ca2+-activated K+ channels in the modulation of 4-aminopyridine-induced burst firing in rat cerebellar Purkinje cells. Brain Res 1156:59–66PubMedGoogle Scholar
  117. Yokoyama CT, Westenbroek RE, Hell JW, Soong TW, Snutch TP, Catterall WA (1995) Biochemical properties and subcellular distribution of the neuronal class E calcium channel α1 subunit. J Neurosci 15:6419–6432PubMedGoogle Scholar
  118. Yunker AM, Sharp AH, Sundarraj S, Ranganathan V, Copeland TD, McEnery MW (2003) Immunological characterization of T-type voltage-dependent calcium channel CaV3.1α1G and CaV3.3α1I isoforms reveal differences in their localization, expression, and neural development. Neuroscience 117:321–335PubMedGoogle Scholar
  119. Zucca S, Valenzuela CF (2010) Low concentrations of alcohol inhibit BDNF-dependent GABAergic plasticity via L-type Ca2+ channel inhibition in developing CA3 hippocampal pyramidal neurons. J Neurosci 30:6778–6781Google Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PediatricsGeorgetown University Medical CenterWashington, DCUSA

Personalised recommendations