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T-Type Calcium Channels and Epilepsy

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Pathologies of Calcium Channels

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Abstract

Epilepsy is characterized by spontaneous recurrent seizures in which electrical activity in particular brain regions becomes over-excitable. As different brain regions interact in cycle, one excites the next until they become locked into a self-propagating loop. Low voltage-activated T-type calcium channels underlie the burst-firing associated with spike-and-wave discharges observed on electroencephalography recordings during certain forms of epileptic seizures. It is currently estimated that around 50 million people in the world suffer from epilepsy. Of these, around 30 % of patients are resistant to current medications and up to 90 % of treatable patients experience significant side effects of the drugs. As such, there is considerable need for new approaches towards the development of novel efficacious therapeutics with fewer side effects.

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References

  • Adams PJ, Snutch TP (2007) Calcium channelopathies: voltage-gated calcium channels. Subcell Biochem 45:215–251

    PubMed  CAS  Google Scholar 

  • Akaike N, Kostyuk PG, Osipchuk YV (1989) Dihydropyridine-sensitive low-threshold calcium channels in isolated rat hypothalamic neurones. J Physiol 412:181–195

    PubMed  CAS  Google Scholar 

  • Akman O, Demiralp T, Ates N, Onat FY (2010) Electroencephalographic differences between WAG/Rij and GAERS rat models of absence epilepsy. Epilepsy Res 89:185–193

    PubMed  Google Scholar 

  • Becker AJ, Pitsch J, Sochivko D, Opitz T, Staniek M, Chen CC, Campbell KP, Schoch S, Yaari Y, Beck H (2008) Transcriptional upregulation of Cav3.2 mediates epileptogenesis in the pilocarpine model of epilepsy. J Neurosci 28:13341–13353

    PubMed  CAS  Google Scholar 

  • Berrow NS, Brice NL, Tedder I, Page KM, Dolphin AC (1997) Properties of cloned rat alpha1A calcium channels transiently expressed in the COS-7 cell line. Eur J Neurosci 9:739–748

    PubMed  CAS  Google Scholar 

  • Biton V (2007) Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol 30:230–240

    PubMed  CAS  Google Scholar 

  • Bourinet E, Alloui A, Monteil A, Barrère C, Couette B, Poirot O, Pages A, McRory J, Snutch TP, Eschalier A, Nargeot J (2005) Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J 24:315–324

    PubMed  CAS  Google Scholar 

  • Broicher T, Seidenbecher T, Meuth P, Munsch T, Meuth SG, Kanyshkova T, Pape HC, Budde T (2007) T-current related effects of antiepileptic drugs and a Ca2 + channel antagonist on thalamic relay and local circuit interneurons in a rat model of absence epilepsy. Neuropharmacology 53:431–446

    PubMed  CAS  Google Scholar 

  • Broicher T, Kanyshkova T, Meuth P, Pape HC, Budde T (2008) Correlation of T-channel coding gene expression, IT, and the low threshold Ca2 + spike in the thalamus of a rat model of absence epilepsy. Mol Cell Neurosci 39:384–399

    PubMed  CAS  Google Scholar 

  • Browne TR, Dreifuss FE, Dyken PR, Goode DJ, Penry JK, Porter RJ, White BG, White PT (1975) Ethosuximide in the treatment of absence (peptit mal) seizures. Neurology 25:515–524

    PubMed  CAS  Google Scholar 

  • Cain SM, Snutch TP (2010) Contributions of T-type calcium channel isoforms to neuronal firing. Channels 4:44–51

    Google Scholar 

  • Cain SM, Snutch TP (2011) Voltage-gated calcium channels and disease. Biofactors Oxf Engl 37:197–205

    CAS  Google Scholar 

  • Cain SM, Snutch TP (2013) T-type calcium channels in burst-firing, network synchrony, and epilepsy. Biochim Biophys Acta 1828:1572–1578

    PubMed  CAS  Google Scholar 

  • Carter AG, Sabatini BL (2004) State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44:483–493

    PubMed  CAS  Google Scholar 

  • Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57:411–425

    PubMed  CAS  Google Scholar 

  • Cavalheiro EA (1995) The pilocarpine model of epilepsy. Ital J Neurol Sci 16:33–37

    PubMed  CAS  Google Scholar 

  • Cavalheiro EA, Santos NF, Priel MR (1996) The pilocarpine model of epilepsy in mice. Epilepsia 37:1015–1019

    PubMed  CAS  Google Scholar 

  • Chemin J, Monteil A, Bourinet E, Nargeot J, Lory P (2001) Alternatively spliced alpha(1G) (Ca(V)3.1) intracellular loops promote specific T-type Ca(2 +) channel gating properties. Biophys J 80:1238–1250

    PubMed  CAS  Google Scholar 

  • Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z, Ding K, Lo WH, Qiang B, Chan P, Shen Y, Wu X (2003) Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol 54:239–243

    PubMed  CAS  Google Scholar 

  • Chen SD, Yeh KH, Huang YH, Shaw FZ (2011) Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges. Epilepsia 52:1311–1318

    PubMed  CAS  Google Scholar 

  • Cheong E, Lee S, Choi BJ, Sun M, Lee CJ, Shin HS (2008) Tuning thalamic firing modes via simultaneous modulation of T- and L-type Ca2 + channels controls pain sensory gating in the thalamus. J. Neurosci. Off. J. Soc. Neurosci. 28:13331–13340

    CAS  Google Scholar 

  • Cheong E, Zheng Y, Lee K, Lee J, Kim S, Sanati M, Lee S, Kim YS, Shin HS (2009) Deletion of phospholipase C beta4 in thalamocortical relay nucleus leads to absence seizures. Proc Natl Acad Sci U S 106:21912–21917

    CAS  Google Scholar 

  • Chevalier M, Lory P, Mironneau C, Macrez N, Quignard JF (2006) T-type Cav3.3 calcium channels produce spontaneous low-threshold action potentials and intracellular calcium oscillations. Eur J Neurosci 23:2321–2329

    PubMed  Google Scholar 

  • Chuang RS, Jaffe H, Cribbs L, Perez-Reyes E, Swartz KJ (1998) Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nat Neurosci 1:668–674

    PubMed  CAS  Google Scholar 

  • Coenen AM, Van Luijtelaar EL (2003) Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats. Behav Genet 33:635–655

    PubMed  CAS  Google Scholar 

  • Contreras D (2006) The role of T-channels in the generation of thalamocortical rhythms. CNS Neurol Disord: Drug Targets 5:571–585

    CAS  Google Scholar 

  • Coulter DA, Huguenard JR, Prince DA (1989a) Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons. Neurosci Lett 98:74–78

    PubMed  CAS  Google Scholar 

  • Coulter DA, Huguenard JR, Prince DA (1989b) Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol 25:582–593

    PubMed  CAS  Google Scholar 

  • 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 11:2949–2964

    PubMed  CAS  Google Scholar 

  • Crunelli V, Leresche N (2002) Block of Thalamic T-Type Ca(2 +) Channels by Ethosuximide Is Not the Whole Story. Epilepsy Curr 2:53–56

    PubMed  Google Scholar 

  • David LS, Garcia E, Cain SM, Thau E, Tyson JR, Snutch TP (2010) Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development. Channels (Austin) 4:375–389

    CAS  Google Scholar 

  • De Curtis M, Radici C, Forti M (1999) Cellular mechanisms underlying spontaneous interictal spikes in an acute model of focal cortical epileptogenesis. Neuroscience 88:107–117

    PubMed  Google Scholar 

  • Diana MA, Otsu Y, Maton G, Collin T, Chat M, Dieudonné S (2007) T-type and L-type Ca2 + conductances define and encode the bimodal firing pattern of vestibulocerebellar unipolar brush cells. J Neurosci 27:3823–3838

    PubMed  CAS  Google Scholar 

  • 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 30:99–109

    PubMed  CAS  Google Scholar 

  • Emerick MC, Stein R, Kunze R, McNulty MM, Regan MR, Hanck DA, Agnew WS (2006) Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations. Proteins 64:320–342

    PubMed  CAS  Google Scholar 

  • Ernst WL, Zhang Y, Yoo JW, Ernst SJ, Noebels JL (2009) Genetic enhancement of thalamocortical network activity by elevating alpha 1 g-mediated low-voltage-activated calcium current induces pure absence epilepsy. J Neurosci 29:1615–1625

    PubMed  CAS  Google Scholar 

  • Errington AC, Renger JJ, Uebele VN, Crunelli V (2010) State-dependent firing determines intrinsic dendritic Ca2 + signaling in thalamocortical neurons. J Neurosci 30:14843–14853

    PubMed  CAS  Google Scholar 

  • Faas GC, Vreugdenhil M, Wadman WJ (1996) Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat. Neuroscience 75:57–67

    PubMed  CAS  Google Scholar 

  • Fox AP, Nowycky MC, Tsien RW (1987) Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol 394:149–172

    PubMed  CAS  Google Scholar 

  • Gomora JC, Daud AN, Weiergräber M, Perez-Reyes E (2001) Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol 60:1121–1132

    PubMed  CAS  Google Scholar 

  • Graef JD, Nordskog BK, Wiggins WF, Godwin DW (2009) An acquired channelopathy involving thalamic T-type Ca2 + channels after status epilepticus. J Neurosci 29:4430–4441

    PubMed  CAS  Google Scholar 

  • Gülhan Aker R, Tezcan K, Carçak N, Sakalli E, Akin D, Onat FY (2009) Localized cortical injections of ethosuximide suppress spike-and-wave activity and reduce the resistance to kindling in genetic absence epilepsy rats (GAERS). Epilepsy Res 89:7–16

    PubMed  Google Scholar 

  • Heron SE, Khosravani H, Varela D, Bladen C, Williams TC, Newman MR, Scheffer IE, Berkovic SF, Mulley JC, Zamponi GW (2007) Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants. Ann Neurol 62:560–568

    PubMed  CAS  Google Scholar 

  • Herrington J, Lingle CJ (1992) Kinetic and pharmacological properties of low voltage-activated Ca2 + current in rat clonal (GH3) pituitary cells. J Neurophysiol 68:213–232

    PubMed  CAS  Google Scholar 

  • Huang Z, Lujan R, Kadurin I, Uebele VN, Renger JJ, Dolphin AC, Shah MM (2011) Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses. Nat Neurosci 14:478–486

    PubMed  CAS  Google Scholar 

  • Hughes SW, Crunelli V (2005) Thalamic mechanisms of EEG alpha rhythms and their pathological implications. Neuroscientist 11:357–372

    PubMed  Google Scholar 

  • Hughes SW, Crunelli V (2007) Just a phase they’re going through: the complex interaction of intrinsic high-threshold bursting and gap junctions in the generation of thalamic alpha and theta rhythms. Int J Psychophysiol 64:3–17

    PubMed  Google Scholar 

  • Huguenard JR (1996) Low-threshold calcium currents in central nervous system neurons. Annu Rev Physiol 58:329–348

    PubMed  CAS  Google Scholar 

  • Isope P, Murphy TH (2005) Low threshold calcium currents in rat cerebellar Purkinje cell dendritic spines are mediated by T-type calcium channels. J Physiol 562:257–269

    PubMed  CAS  Google Scholar 

  • Jacus MO, Uebele VN, Renger JJ, Todorovic SM (2012) Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons. J Neurosci 32:9374–9382

    PubMed  CAS  Google Scholar 

  • Jiruska P, de Curtis M, Jefferys JG, Schevon CA, Schiff SJ, Schindler K (2013) Synchronization and desynchronization in epilepsy: controversies and hypotheses. J Physiol 591:787–797

    PubMed  CAS  Google Scholar 

  • Joksovic PM, Bayliss DA, Todorovic SM (2005) Different kinetic properties of two T-type Ca2 + currents of rat reticular thalamic neurones and their modulation by enflurane. J Physiol 566:125–142

    PubMed  CAS  Google Scholar 

  • Kavalali ET, Zhuo M, Bito H, Tsien RW (1997) Dendritic Ca2 + channels characterized by recordings from isolated hippocampal dendritic segments. Neuron 18:651–663

    PubMed  CAS  Google Scholar 

  • Kelly KM, Gross RA, Macdonald RL (1990) Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons. Neurosci Lett 116:233–238

    PubMed  CAS  Google Scholar 

  • Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW, Shin HS (2001) Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca2 + channels. Neuron 31:35–45

    PubMed  CAS  Google Scholar 

  • Kito M, Maehara M, Watanabe K (1996) Mechanisms of T-type calcium channel blockade by zonisamide. Seizure 5:115–119

    PubMed  CAS  Google Scholar 

  • 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 11:4171–4178

    PubMed  Google Scholar 

  • Kostyuk PG, Molokanova EA, Pronchuk NF, Savchenko AN, Verkhratsky AN (1992) Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons. Neuroscience 51:755–758

    PubMed  CAS  Google Scholar 

  • Kraus RL, Li Y, Gregan Y, Gotter AL, Uebele VN, Fox SV, Doran SM, Barrow JC, Yang ZQ, Reger TS, Koblan KS, Renger JJ (2010) In vitro characterization of T-type calcium channel antagonist TTA-A2 and in vivo effects on arousal in mice. J Pharmacol Exp Ther 335:409–417

    PubMed  CAS  Google Scholar 

  • Kumar PP, Stotz SC, Paramashivappa R, Beedle AM, Zamponi GW, Rao AS (2002) Synthesis and evaluation of a new class of nifedipine analogs with T-type calcium channel blocking activity. Mol Pharmacol 61:649–658

    PubMed  CAS  Google Scholar 

  • Kwan P, Sills GJ, Brodie MJ (2001) The mechanisms of action of commonly used antiepileptic drugs. Pharmacol Ther 90:21–34

    PubMed  CAS  Google Scholar 

  • Lee JH, Gomora JC, Cribbs LL, Perez-Reyes E (1999) Nickel block of three cloned T-type calcium channels: low concentrations selectively block alpha1H. Biophys J 77:3034–3042

    PubMed  CAS  Google Scholar 

  • Leresche N, Parri HR, Erdemli G, Guyon A, Turner JP, Williams SR, Asprodini E, Crunelli V (1998) On the action of the anti-absence drug ethosuximide in the rat and cat thalamus. J Neurosci 18:4842–4853

    PubMed  CAS  Google Scholar 

  • Liang J, Zhang Y, Chen Y, Wang J, Pan H, Wu H, Xu K, Liu X, Jiang Y, Shen Y, Wu X (2007) Common polymorphisms in the CACNA1H gene associated with childhood absence epilepsy in Chinese Han population. Ann Hum Genet 71:325–335

    PubMed  CAS  Google Scholar 

  • Lisman JE (1997) Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci 20:38–43

    PubMed  CAS  Google Scholar 

  • Llinas R, Yarom Y (1981) Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances. J Physiol 315:549–567

    PubMed  CAS  Google Scholar 

  • Magee JC, Johnston D (1995) Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268:301–304

    PubMed  CAS  Google Scholar 

  • Manning JP, Richards DA, Leresche N, Crunelli V, Bowery NG (2004) Cortical-area specific block of genetically determined absence seizures by ethosuximide. Neuroscience 123:5–9

    PubMed  CAS  Google Scholar 

  • Marescaux C, Vergnes M, Depaulis A (1992) Genetic absence epilepsy in rats from Strasbourg-a review. J Neural Transm Suppl 35:37–69

    PubMed  CAS  Google Scholar 

  • Markram H, Sakmann B (1994) Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc Natl Acad Sci U S 91:5207–5211

    CAS  Google Scholar 

  • Massie BM (1997) Mibefradil: a selective T-type calcium antagonist. Am J Cardiol 80:23I–32I

    PubMed  CAS  Google Scholar 

  • Massie BM (1998) Mibefradil, a T-type channel-selective calcium antagonist: clinical trials in chronic stable angina pectoris. Am J Hypertens 11:95S–102S

    PubMed  CAS  Google Scholar 

  • Matar N, Jin W, Wrubel H, Hescheler J, Schneider T, Weiergräber M (2009) Zonisamide block of cloned human T-type voltage-gated calcium channels. Epilepsy Res 83:224–234

    PubMed  CAS  Google Scholar 

  • McCormick DA, Contreras D (2001) On the cellular and network bases of epileptic seizures. Annu Rev Physiol 63:815–846

    PubMed  CAS  Google Scholar 

  • McDonough SI, Bean BP (1998) Mibefradil inhibition of T-type calcium channels in cerebellar purkinje neurons. Mol Pharmacol 54:1080–1087

    PubMed  CAS  Google Scholar 

  • McKay BE, McRory JE, Molineux ML, Hamid J, Snutch TP, Zamponi GW, Turner RW (2006) Ca(V)3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur J Neurosci 24:2581–2594

    PubMed  Google Scholar 

  • McRory JE, Santi CM, Hamming KS, Mezeyova J, Sutton KG, Baillie DL, Stea A, Snutch TP (2001) Molecular and functional characterization of a family of rat brain T-type calcium channels. J Biol Chem 276:3999–4011

    PubMed  CAS  Google Scholar 

  • Mittman S, Guo J, Emerick MC, Agnew WS (1999) Structure and alternative splicing of the gene encoding alpha1I, a human brain T calcium channel alpha1 subunit. Neurosci Lett 269:121–124

    PubMed  CAS  Google Scholar 

  • Monteil A, Chemin J, Bourinet E, Mennessier G, Lory P, Nargeot J (2000) Molecular and functional properties of the human alpha(1G) subunit that forms T-type calcium channels. J Biol Chem 275:6090–6100

    PubMed  CAS  Google Scholar 

  • Mudado MA, Rodrigues AL, Prado VF, Beirão PS, Cruz JS (2004) Cav 3.1 and Cav 3.3 account for T-type Ca2 + current in GH3 cells. Braz J Med Biol Res 37:929–935

    PubMed  CAS  Google Scholar 

  • Murbartián J, Arias JM, Perez-Reyes E (2004) Functional impact of alternative splicing of human T-type Cav3.3 calcium channels. J Neurophysiol 92:3399–3407

    PubMed  Google Scholar 

  • Perez-Reyes E (2003) Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 83:117–161

    PubMed  CAS  Google Scholar 

  • Pinault D, Leresche N, Charpier S, Deniau JM, Marescaux C, Vergnes M, Crunelli V (1998) Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy. J Physiol 509:449–456

    PubMed  CAS  Google Scholar 

  • Pinault D, Vergnes M, Marescaux C (2001) Medium-voltage 5-9-Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons. Neuroscience 105:181–201

    PubMed  CAS  Google Scholar 

  • Polack PO, Charpier S (2009) Ethosuximide converts ictogenic neurons initiating absence seizures into normal neurons in a genetic model. Epilepsia 50:1816–1820

    PubMed  CAS  Google Scholar 

  • Polack PO, Guillemain I, Hu E, Deransart C, Depaulis A, Charpier S (2007) Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures. J Neurosci 27:6590–6599

    PubMed  CAS  Google Scholar 

  • Polack PO, Mahon S, Chavez M, Charpier S (2009) Inactivation of the Somatosensory Cortex Prevents Paroxysmal Oscillations in Cortical and Related Thalamic Neurons in a Genetic Model of Absence Epilepsy. Cereb Cortex 19:2078–2091

    PubMed  Google Scholar 

  • Powell KL, Cain SM, Ng C, Sirdesai S, David LS, Kyi M, Garcia E, Tyson JR, Reid CA, Bahlo M, Foote SJ, Snutch TP, O’Brien TJ (2009) A Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. J Neurosci 29:371–380

    PubMed  CAS  Google Scholar 

  • Randall AD, Tsien RW (1997) Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels. Neuropharmacology 36:879–893

    PubMed  CAS  Google Scholar 

  • Reinagel P, Godwin D, Sherman SM, Koch C (1999) Encoding of visual information by LGN bursts. J Neurophysiol 81:2558–2569

    PubMed  CAS  Google Scholar 

  • Richards DA, Manning JP, Barnes D, Rombola L, Bowery NG, Caccia S, Leresche N, Crunelli V (2003) Targeting thalamic nuclei is not sufficient for the full anti-absence action of ethosuximide in a rat model of absence epilepsy. Epilepsy Res 54:97–107

    PubMed  CAS  Google Scholar 

  • Rogawski MA, Porter RJ (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev 42:223–286

    PubMed  CAS  Google Scholar 

  • Sanabria ER, Su H, Yaari Y (2001) Initiation of network bursts by Ca2 + -dependent intrinsic bursting in the rat pilocarpine model of temporal lobe epilepsy. J Physiol 532:205–216

    PubMed  CAS  Google Scholar 

  • Sayer RJ, Brown AM, Schwindt PC, Crill WE (1993) Calcium currents in acutely isolated human neocortical neurons. J Neurophysiol 69:1596–1606

    PubMed  CAS  Google Scholar 

  • Sherman SM (2001) Tonic and burst firing: dual modes of thalamocortical relay. Trends Neurosci 24:122–126

    PubMed  CAS  Google Scholar 

  • Shipe WD, Barrow JC, Yang ZQ, Lindsley CW, Yang FV, Schlegel KA, Shu Y, Rittle KE, Bock MG, Hartman GD, Tang C, Ballard JE, Kuo Y, Adarayan ED, Prueksaritanont T, Zrada MM, Uebele VN, Nuss CE, Connolly TM, Doran SM, Fox SV, Kraus RL, Marino MJ, Graufelds VK, Vargas HM, Bunting PB, Hasbun-Manning M, Evans RM, Koblan KS, Renger JJ (2008) Design, synthesis, and evaluation of a novel 4-aminomethyl-4-fluoropiperidine as a T-type Ca2 + channel antagonist. J Med Chem 51:3692–3695

    PubMed  CAS  Google Scholar 

  • Sidach SS, Mintz IM (2002) Kurtoxin, a gating modifier of neuronal high- and low-threshold ca channels. J Neurosci 22:2023–2034

    PubMed  CAS  Google Scholar 

  • Singh B, Monteil A, Bidaud I, Sugimoto Y, Suzuki T, Hamano S, Oguni H, Osawa M, Alonso ME, Delgado-Escueta AV, Inoue Y, Yasui-Furukori N, Kaneko S, Lory P, Yamakawa K (2007) Mutational analysis of CACNA1G in idiopathic generalized epilepsy. Hum Mutat 28:524–525

    PubMed  Google Scholar 

  • Slaght SJ, Leresche N, Deniau JM, Crunelli V, Charpier S (2002) Activity of thalamic reticular neurons during spontaneous genetically determined spike and wave discharges. J Neurosci 22:2323–2334

    PubMed  CAS  Google Scholar 

  • Su H, Sochivko D, Becker A, Chen J, Jiang Y, Yaari Y, Beck H (2002) Upregulation of a T-type Ca2 + channel causes a long-lasting modification of neuronal firing mode after status epilepticus. J Neurosci 22:3645–3655

    PubMed  CAS  Google Scholar 

  • Suzuki S, Rogawski MA (1989) T-type calcium channels mediate the transition between tonic and phasic firing in thalamic neurons. Proc Natl Acad Sci U S A 86:7228–7232

    PubMed  CAS  Google Scholar 

  • Suzuki S, Kawakami K, Nishimura S, Watanabe Y, Yagi K, Seino M, Miyamoto K (1992) Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 12:21–27

    PubMed  CAS  Google Scholar 

  • Tai C, Kuzmiski JB, MacVicar BA (2006) Muscarinic enhancement of R-type calcium currents in hippocampal CA1 pyramidal neurons. J Neurosci 26:6249–6258

    PubMed  CAS  Google Scholar 

  • 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 19:1895–1911

    PubMed  CAS  Google Scholar 

  • Talley EM, Solórzano G, Depaulis A, Perez-Reyes E, Bayliss DA (2000) Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat. Brain Res Mol Brain Res 75:159–165

    PubMed  CAS  Google Scholar 

  • Tang AH, Karson MA, Nagode DA, McIntosh JM, Uebele VN, Renger JJ, Klugmann M, Milner TA, Alger BE (2011) Nerve terminal nicotinic acetylcholine receptors initiate quantal GABA release from perisomatic interneurons by activating axonal T-type (Cav3) Ca2+ channels and Ca2+ release from stores. J Neurosci 31:13546–13561

    PubMed  CAS  Google Scholar 

  • Tennigkeit F, Schwarz DW, Puil E (1998) Modulation of bursts and high-threshold calcium spikes in neurons of rat auditory thalamus. Neuroscience 83:1063–1073

    PubMed  CAS  Google Scholar 

  • Timofeev I, Steriade M (1998) Cellular mechanisms underlying intrathalamic augmenting responses of reticular and relay neurons. J Neurophysiol 79:2716–2729

    PubMed  CAS  Google Scholar 

  • Todorovic SM, Jevtovic-Todorovic V (2013) Neuropathic pain: role for presynaptic T-type channels in nociceptive signaling. Pflugers Arch. doi:10.1007/s00424-012-1211-y

    PubMed  Google Scholar 

  • Todorovic SM, Lingle CJ (1998) Pharmacological properties of T-type Ca2 + current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents. J Neurophysiol 79:240–252

    PubMed  CAS  Google Scholar 

  • Tringham E, Powell KL, Cain SM, Kuplast K, Mezeyova J, Weerapura M, Eduljee C, Jiang X, Smith P, Morrison JL, Jones NC, Braine E, Rind G, Fee-Maki M, Parker D, Pajouhesh H, Parmar M, O’Brien TJ, Snutch TP (2012) T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures. Sci Transl Med 4:121ra19

    Google Scholar 

  • Tryba AK, Kaczorowski CC, Ben-Mabrouk F, Elsen FP, Lew SM, Marcuccilli CJ (2011) Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric patients with epilepsy. Eur J Neurosci 34:31–44

    PubMed  Google Scholar 

  • Tsakiridou E, Bertollini L, de Curtis M, Avanzini G, Pape HC (1995) Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J Neurosci 15:3110–3117

    PubMed  CAS  Google Scholar 

  • Twombly DA, Yoshii M, Narahashi T (1988) Mechanisms of calcium channel block by phenytoin. J Pharmacol Exp Ther 246:189–195

    PubMed  CAS  Google Scholar 

  • Uebele VN, Nuss CE, Fox SV, Garson SL, Cristescu R, Doran SM, Kraus RL, Santarelli VP, Li Y, Barrow JC, Yang ZQ, Schlegel KA, Rittle KE, Reger TS, Bednar RA, Lemaire W, Mullen FA, Ballard JE, Tang C, Dai G, McManus OB, Koblan KS, Renger JJ (2009) Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys 55:81–93

    PubMed  CAS  Google Scholar 

  • Viana F, Van den Bosch L, Missiaen L, Vandenberghe W, Droogmans G, Nilius B, Robberecht W (1997) Mibefradil (Ro 40-5967) blocks multiple types of voltage-gated calcium channels in cultured rat spinal motoneurones. Cell Calcium 22:299–311

    PubMed  CAS  Google Scholar 

  • Weiergräber M, Stephani U, Köhling R (2010) Voltage-gated calcium channels in the etiopathogenesis and treatment of absence epilepsy. Brain Res Rev 62:245–271

    PubMed  Google Scholar 

  • Welker HA, Wiltshire H, Bullingham R (1998) Clinical pharmacokinetics of mibefradil. Clin Pharmacokinet 35:405–423

    PubMed  CAS  Google Scholar 

  • Wellmer J, Su H, Beck H, Yaari Y (2002) Long-lasting modification of intrinsic discharge properties in subicular neurons following status epilepticus. Eur J Neurosci 16:259–266

    PubMed  Google Scholar 

  • Williams SR, Tóth TI, Turner JP, Hughes SW, Crunelli V (1997) The “window” component of the low threshold Ca2 + current produces input signal amplification and bistability in cat and rat thalamocortical neurones. J Physiol 505:689–705

    PubMed  CAS  Google Scholar 

  • Wolfart J, Roeper J (2002) Selective coupling of T-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons. J Neurosci 22:3404–3413

    PubMed  CAS  Google Scholar 

  • Yaari Y, Yue C, Su H (2007) Recruitment of apical dendritic T-type Ca2 + channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis. J Physiol 580:435–450

    PubMed  CAS  Google Scholar 

  • Yang ZQ, Barrow JC, Shipe WD, Schlegel KA, Shu Y, Yang FV, Lindsley CW, Rittle KE, Bock MG, Hartman GD, Uebele VN, Nuss CE, Fox SV, Kraus RL, Doran SM, Connolly TM, Tang C, Ballard JE, Kuo Y, Adarayan ED, Prueksaritanont T, Zrada MM, Marino MJ, Graufelds VK, DiLella AG, Reynolds IJ, Vargas HM, Bunting PB, Woltmann RF, Magee MM, Koblan KS, Renger JJ (2008) Discovery of 1,4-substituted piperidines as potent and selective inhibitors of T-type calcium channels. J Med Chem 51:6471–6477

    PubMed  CAS  Google Scholar 

  • Yunker AM (2003) Modulation and pharmacology of low voltage-activated (“T-Type”) calcium channels. J Bioenerg Biomembr 35:577–598

    PubMed  CAS  Google Scholar 

  • Yunker AM, McEnery MW (2003) Low-voltage-activated (“T-Type”) calcium channels in review. J Bioenerg Biomembr 35:533–575

    PubMed  CAS  Google Scholar 

  • Zamponi GW, Bourinet E, Snutch TP (1996) Nickel block of a family of neuronal calcium channels: subtype- and subunit-dependent action at multiple sites. J Membr Biol 151:77–90

    PubMed  CAS  Google Scholar 

  • Zamponi GW, Lory P, Perez-Reyes E (2009) Role of voltage-gated calcium channels in epilepsy. Pflugers Arch 460:395–403

    PubMed  Google Scholar 

  • Zhang Y, Mori M, Burgess DL, Noebels JL (2002) Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J Neurosci 22:6362–6371

    PubMed  CAS  Google Scholar 

  • Zheng TW, O’Brien TJ, Morris MJ, Reid CA, Jovanovska V, O’Brien P, van Raay L, Gandrathi AK, Pinault D (2012) Rhythmic neuronal activity in S2 somatosensory and insular cortices contribute to the initiation of absence-related spike-and-wave discharges. Epilepsia 53:1948–1958

    PubMed  Google Scholar 

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Acknowledgments

T. P. Snutch is supported by an operating grant from the Canadian Institutes of Health Research (#10677) and a Canada Research Chair in Biotechnology and Genomics-Neurobiology. S. M. Cain received support from the B.C. Epilepsy Society and the Michael Smith Foundation for Health Research.

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Authors and Affiliations

  1. Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada

    Stuart M. Cain & Terrance P. Snutch

  2. Department of Neuroscience, Carleton University, Ottawa, ON, Canada

    Michael E. Hildebrand

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  1. Stuart M. Cain
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  2. Michael E. Hildebrand
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  3. Terrance P. Snutch
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Correspondence to Terrance P. Snutch .

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  1. Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada

    Norbert Weiss

  2. Department of Neurophysiology and Pharmacology, Medical University Vienna, Vienna, Austria

    Alexandra Koschak

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Cain, S.M., Hildebrand, M.E., Snutch, T.P. (2014). T-Type Calcium Channels and Epilepsy . In: Weiss, N., Koschak, A. (eds) Pathologies of Calcium Channels. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_4

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