Abstract
One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological diseases. This review addresses the mutations underlying familial hemiplegic migraine (FHM) with particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca2+ channel FHM type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of Cav2.1 channels. FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an increased open probability. These biophysical alterations may lead to a gain-of-function on synaptic transmission depending upon factors such as action potential waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM knock-in mouse models has demonstrated a deficient regulation of the cortical excitation/inhibition (E/I) balance. The resulting excessive increases in cortical excitation may be the mechanisms that underlie abnormal sensory processing together with an increase in the susceptibility to cortical spreading depression (CSD). Increasing evidence from FHM KI animal studies support the idea that CSD, the underlying mechanism of aura, can activate trigeminal nociception, and thus trigger the headache mechanisms.
Similar content being viewed by others
References
Adams PJ, Garcia E, David LS, Mulatz KJ, Spacey SD, Snutch TP (2009) Ca(V)2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: implications for calcium channelopathies. Channels (Austin) 3:110–121
Adams PJ, Rungta RL, Garcia E, van den Maagdenberg AM, MacVicar BA, Snutch TP (2010) Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel. Proc Natl Acad Sci USA 107:18694–18699
Ali AB, Nelson C (2006) Distinct Ca2+ channels mediate transmitter release at excitatory synapses displaying different dynamic properties in rat neocortex. Cereb Cortex 16:386–393
Ali AB, Bannister AP, Thomson AM (2007) Robust correlations between action potential duration and the properties of synaptic connections in layer 4 interneurones in neocortical slices from juvenile rats and adult rat and cat. J Physiol 580:149–169
Alonso I, Barros J, Tuna A, Seixas A, Coutinho P, Sequeiros J, Silveira I (2004) A novel R1347Q mutation in the predicted voltage sensor segment of the P/Q-type calcium-channel alpha-subunit in a family with progressive cerebellar ataxia and hemiplegic migraine. Clin Genet 65:70–72
Anttila V, Wessman M, Kallela M, Palotie A (2011) Towards an understanding of genetic predisposition to migraine. Genome Med 3(3):17
Aosaki T, Kasai H (1989) Characterization of two kinds of high-voltage-activated Ca-channel currents in chick sensory neurons. Differential sensitivity to dihydropyridines and omega-conotoxin GVIA. Pflugers Arch 414:150–156
Atluri PP, Regehr WG (1996) Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse. J Neurosci 16:5661–5671
Ayata C (2010) Cortical spreading depression triggers migraine attack: pro. Headache 50:725–730
Barrett CF, Cao YQ, Tsien RW (2005) Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. J Biol Chem 280:24064–24071
Bisagno V, Raineri M, Peskin V, Wikinski SI, Uchitel OD, Llinás RR, Urbano FJ (2010) Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice. Psychopharmacology (Berl) 212(2):205–214
Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8:136–142
Bollmann JH, Sakmann B, Borst JGG (2000) Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289:953–957
Borst JGG, Sakmann B (1998) Calcium current during a single action potential in a large presynaptic terminal of the rat brainstem. J Physiol 506:143–157
Borst JG, Sakmann B (1999) Effect of changes in action potential shape on calcium currents and transmitter release in a calyx-type synapse of the rat auditory brainstem. Philos Trans R Soc Lond B 354:347–355
Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM (2001) Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Ann Neurol 50:582–587
Brennan KC, Bates EA, Shapiro RE, Zyuzin J, Hallows WC, Huang Y, Lee H-Y, Jones CR, Fu Y-H, Charles AC, Ptáček LJ (2013) Casein kinase Iδ mutations in familial migraine and advanced sleep phase. Sci Transl Med 5(183):183ra56. 1–11
Cao YQ, Tsien RW (2005) Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. Proc Natl Acad Sci USA 102:2590–2595
Cao YQ, Piedras-Renteria ES, Smith GB, Chen G, Harata NC, Tsien RW (2004) Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. Neuron 43:387–400
Catterall WA (1998) Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. Cell Calcium 24:307–323
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555
Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947
Catterall WA, Few AP (2008) Calcium channel regulation and presynaptic plasticity. Neuron 59:882–901
Catterall WA, Dib-Hajj S, Meisler MH, Pietrobon D (2008) Inherited neuronal ion channelopathies: new windows on complex neurological diseases. J Neurosci 28:11768–11777
Catterall WA, Kalume F, Oakley JC (2010) NaV1.1 channels and epilepsy. J Physiol 588:1849–1859
Cestèle S, Scalmani P, Rusconi R, Terragni B, Franceschetti S, Mantegazza M (2008) Self-limited hyperexcitability: functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ channel. J Neurosci 28:7273–7283
Chan YC et al (2008) Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation. J Clin Neurosci 15:891–894
Chanda ML et al (2013) Behavioral evidence for photophobia and stress-related ipsilateral head pain in transgenic. Cacna1a mutant mice. Pain 154(2013):1254–1262
Charles A (2010) Does cortical spreading depression initiate a migraine attack? Maybe not. Headache 50:731–733
Chasman DI, Schurks M, Anttila V, de Vries B, Schminke U, Launer LJ, Terwindt GM, van den Maagdenberg AM, Fendrich K, Volzke H, Ernst F, Griffiths LR, Buring JE, Kallela M, Freilinger T, Kubisch C, Ridker PM, Palotie A, Ferrari MD, Hoffmann W, Zee RY, Kurth T (2011) Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet 43(7):695–698
Chaudhuri D, Issa JB, Yue DT (2007) Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels. J Gen Physiol 129:385–401
Cholet N et al (2002) Similar perisynaptic glial localization for the Na+, K+ −ATPase α2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex 12:515–525
Cuenca-Leon E, Corominas R, Fernandez-Castillo N, Volpini V, Del Toro M, Roig M, Macaya A, Cormand B (2008) Genetic analysis of 27 Spanish patients with hemiplegic migraine, basilartype migraine and childhood periodic syndromes. Cephalalgia 28:1039–1047
Cuttle MF, Tsujimoto T, Forsythe ID, Takahashi T (1998) Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem. J Physiol 512:723–729
De Fusco M, Marconi R, Silvestri L et al (2003) Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 33:192–196
De Vries B et al (2009) Molecular genetics of migraine. Hum Genet 126:115–132
Deboer T, van Diepen HC, Ferrari MD, Van den Maagdenberg AM, Meijer JH (2013) Reduced sleep and low adenosinergic sensitivity in cacna1a R192Q mutant mice. Sleep 36(1):127–136
Di Guilmi MN, Urbano FJ, González Inchauspe C, Uchitel OD (2011) Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels. J Pharmacol Exp Ther 336(3):973–982
Dichgans M, Freilinger T, Eckstein G et al (2005) Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 366:371–377
Dodge FA, Rahamimoff R (1967) Co-operative action of calcium ions in transmitter release at the neuromuscular junction. J Physiol 193:419–432
Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, Darcel F, Vicaut E, Bousser MG, Tournier-Lasserve E (2001) The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med 345:17–24
Dunlap K, Luebke JI, Turner TJ (1995) Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci 18:89–98
Eikermann-Haerter K, Baum MJ, Ferrari MD, van den Maagdenberg AM, Moskowitz MA, Ayata C (2009a) Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol 66:564–568
Eikermann-Haerter K, Dilekoz E, Kudo C, Savitz SI, Waeber C, Baum MJ, Ferrari MD, van den Maagdenberg AMJM, Moskowitz MA, Ayata C (2009b) Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. J Clin Invest 119:99–109
Eikermann-Haerter K, Yuzawa I, Qin T, Wang Y, Baek K, Kim YR, Hoffmann U, Dilekoz E, Waeber C, Ferrari MD, van den Maagdenberg AM, Moskowitz MA, Ayata C (2011) Enhanced subcortical spreading depression in Familial Hemiplegic Migraine Type 1 mutant mice. J Neurosci 31:5755–5763
Eriksen MK, Thomsen LL, Olesen J (2006) Implications of clinical subtypes of migraine with aura. Headache 46:286–297
Fioretti B et al (2011) Trigeminal ganglion neuron subtype-specific alterations of CaV2.1 calcium current and excitability in a Cacna1a mouse model of migraine. J Physiol 589:5879–5895
Forsythe ID, Tsujimoto T, Barnes-Davies M, Cuttle MF, Takahashi T (1998) Inactivation of presynaptic calcium current contributes to synaptic depression at a fast central synapse. Neuron 20(4):797–807
Gao Z, Todorov B, Barrett CF, van Dorp S, Ferrari MD, van den Maagdenberg AM, De Zeeuw C, Hoebeek FE (2012) Cerebellar ataxia by enhanced Cav2.1 Currents is alleviated by Ca2+-dependent K+-channel activators in Cacna1a S218L mutant mice. J Neurosci 32(44):15533–15546
Giugovaz-Tropper B, Gonzalez-Inchauspe C, Di Guilmi MN, Urbano FJ, Forsythe ID, Uchitel OD (2011) P/Q-type calcium channel ablation in a mice glycinergic synapse mediated by multiple types of Ca(2+) channels alters transmitter release and short term plasticity. Neuroscience 192:219–230
Goadsby PJ (2007) Recent advances in understanding migraine mechanisms, molecules and therapeutics. Trends Mol Med 13:39–44
Goadsby PJ, Lipton RB, Ferrari MD (2002) Migraine- current understanding and treatment. N Engl J Med 346:257–270
González Inchauspe C, Martini FJ, Forsythe ID, Uchitel OD (2004) Functional compensation of P/Q by N-type channels blocks short term plasticity at the calyx of held presynaptic terminal. J Neurosci 24:10379–10383
González Inchauspe C, Forsythe ID, Uchitel OD (2007) Changes in synaptic transmission properties due to the expression of N-type calcium channels at the calyx of Held synapse of mice lacking P/Q-type calcium channels. J Physiol 584:835–851
González Inchauspe C, Urbano FJ, Di Guilmi MN, Forsythe ID, Ferrari MD, van den Maagdenberg AM, Uchitel OD (2010) Gain of function in FHM-1 Ca(V)2.1 knock-in mice is related to the shape of the action potential. J Neurophysiol 104(1):291–299Calcium currents in the presynaptic terminal of the knock –in mice are larger only when activated by a broad action potential, indicating that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission
González Inchauspe C, Urbano FJ, Di Guilmi MN, Ferrari MD, van den Maagdenberg AM, Forsythe ID, Uchitel OD (2012) Presynaptic CaV2.1 calcium chnnels carring familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held. J Neurophysiol 108:2967–2976
Haan J, Kors EE, Vanmolkot KR, van den Maagdenberg AM, Frants RR, Ferrari MD (2005) Migraine genetics: an update. Curr Pain Headache Rep 9:213–220
Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RB et al (2001) Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA 98:4687–4692These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex
Hans M, Luvisetto S, Williams ME, Spagnolo M, Urrutia A, Tottene A, Brust PF, Johnson EC, Harpold MM, Stauderman KA et al (1999) Functional consequences of mutations in the human α1A calcium channel subunit linked to familial hemiplegic migraine. J Neurosci 19:1610–1619
Hennig MH, Postlethwaite M, Forsythe ID, Graham BP (2008) Interactions between multiple sources of short-term plasticity during evoked and spontaneous activity at the rat calyx of Held. J Physiol 586:3129–3146
Hoebeek FE, Stahl JS, van Alphen AM, Schonewille M, Luo C, Rutteman M, van den Maagdenberg AM, Molenaar PC, Goossens HH, Frens MA, De Zeeuw CI (2005) Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron 45:953–965
Iwasaki S, Momiyama A, Uchitel OD, Takahashi T (2000) Developmental changes in calcium channel types mediating central synaptic transmission. J Neurosci 20:59–65
Kahlig KM, Rhodes TH, Pusch M, Freilinger T, Pereira-Monteiro JM, Ferrari MD, van den Maagdenberg AMJM, Dichgans M, George ALG Jr (2008) Divergent sodium channel defects in familial hemiplegic migraine. Proc Natl Acad Sci USA 105:9799–9804
Kaja S, van de Ven RC, Broos LA, Veldman H, van Dijk JG, Verschuuren JJ, Frants RR, Ferrari MD, van den Maagdenberg AM, Plomp JJ (2005) Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness. Neuroscience 135:81–95
Kaja S, Van de Ven RCG, Broos LAM, Frants RR, Ferrari MD, Van den Maagdenberg AMJM, Plomp JJ (2010) Severe and progressive neurotransmitter release aberrations in familial hemiplegic migraine type 1 Cacna1a S218L knock-in mice. J Neurophysiol 104:1445–1455
Karatas H, Erdener SE, Gursoy-Ozdemir Y, Lule S, Eren-Koçak E, Duygu Sen Z, Dalkara T (2013) Spreading depression triggers headache by activating neuronal Panx1 channels. Science 339:1092–1095
Katz E, Ferro PA, Weisz G, Uchitel OD (1996) Calcium channels involved in synaptic transmission at the mature and regenerating mouse neuromuscular junction. J Physiol 497:687–697
Koenderink JB, Zifarelli G, Qiu LY, Schwarz W, De Pont JJ et al (2005) Na, KATPase mutations in familial hemiplegic migraine lead to functional inactivation. Biochim Biophys Acta 1669:61–68
Koester HJ, Sakmann B (2000) Calcium dynamics associated with action potentials in single nerve terminals of pyramidal cells in layer 2/3 of the young rat neocortex. J Physiol 529(Pt 3):625–646
Kors EE, Terwindt GM, Vermeulen FL, Fitzsimons RB, Jardine PE, Heywood P, Love S, van den Maagdenberg AM, Haan J, Frants RR, Ferrari MD (2001) Delayed cerebral edema and fatal coma after minor head trauma: Role of CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol 49:753–760
Kors EE, van den Maagdenberg AM, Plomp JJ, Frants RR, Ferrari MD (2002) Calcium channel mutations and migraine. Curr Opin Neurol 15:311–316
Kors EE, Melberg A, Vanmolkot KR, Kumlien E, Haan J, Raininko R, Flink R, Ginjaar HB, Frants RR, Ferrari MD, van den Maagdenberg AM (2004) Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation. Neurology 63:1136–1137
Kraus RL, Sinnegger MJ, Glossmann H, Hering S, Striessnig J (1998) Familial hemiplegic migraine mutations change alpha1A Ca2+ channel kinetics. J Biol Chem 273:5586–5590
Kraus RL, Sinnegger M, Koschak A, Glossmann H, Stenirri S, Carrera P, Striessnig J (2000) Three New Familial Hemiplegic Migraine Mutants Affect P/Q-type Ca2+ Channel Kinetics. J Biol Chem 275:9239–9243
Lafreniere RG, Cader MZ, Poulin JF, Andres-Enguix I, Simoneau M, Gupta N, Boisvert K, Lafreniere F, McLaughlan S, Dube MP, Marcinkiewicz MM, Ramagopalan S, Ansorge O, Brais B, Sequeiros J, Pereira-Monteiro JM, Griffiths LR, Tucker SJ, Ebers G, Rouleau GA (2010) A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat Med 16(10):1157–1160
Leo L, Gherardini L, Barone V, De Fusco M, Pietrobon D, Pizzorusso T, Casari G (2011) Increased susceptibility to cortical spreading depression in the mouse model of familial hemiplegic migraine type 2. PLoS Genet 7(6):e1002129
Levy D (2010) Migraine pain and nociceptor activation—where do we stand? Headache 50:909–916
Levy D (2012) Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression. Curr Pain Headache Rep 16:270–277
Li L, Bischofberger J, Jonas P (2007) Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons. J Neurosci 27:13420–13429
Liu Z, Ren J, Murphy TH (2003) Decoding of synaptic voltage waveforms by specific classes of recombinant high-threshold Ca2+ channels. J Physiol 553:473–488
Llinás R (1988) The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242:1654–1664
Marconi R, De Fusco M, Aridon P, Plewnia K, Rossi M, Carapelli S et al (2003) Familial hemiplegic migraine type 2 is linked to 0.9 Mb region on chromosome 1q23. Ann Neurol 53:376–381
Marmura MJ, Silberstein SD (2011) Current understanding and treatment of headache disorders: five new things. Neurology 76:S31–S36
Matsushita K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K (2002) Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci 22:4388–4398
Meinrenken CJ, Borst JGG, Sakmann B (2002) Calcium secretion coupling at calyx of held governed by nonuniform channel-vesicle topography. J Neurosci 22:1648–1667
Meinrenken CJ, Borst JG, Sakmann B (2003) Local routes revisited: the space and time dependence of the Ca2+ signal for phasic transmitter release at the rat calyx of Held. J Physiol 547:665–689
Melliti K, Grabner M, Seabrook GR (2003) The familial hemiplegic migraine mutation R192Q reduces G-proteinmediated inhibition of P/Q-type (Ca(V)2.1) calcium channels expressed in human embryonic kidney cells. J Physiol 546:337–347
Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME (1992) P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature 355:827–829
Mochida S, Few AP, Scheuer T, Catterall WA (2008) Regulation of presynaptic Ca(V)2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity. Neuron 57:210–216
Moskowitz MA, Bolay H, Dalkara T (2004) Deciphering migraine mechanisms: clues from familial hemiplegic migraine genotypes. Ann Neurol 55:276–280
Muller M, Felmy F, Schneggenburger R (2008) A limited contribution of Ca2+ current facilitation to paired-pulse facilitation of transmitter release at the rat calyx of Held. J Physiol Lond 586:5503–5520
Mullner C, Broos LA, van den Maagdenberg AM, Striessnig J (2004) Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter Ca2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects. J Biol Chem 279:51844–51850
Newcomb R, Szoke B, Palma A, Wang G, Chen X, Hopkins W, Cong R, Miller J, Urge L, Tarczy-Hornoch K, Loo JA, Dooley DJ, Nadasdi L, Tsien RW, Lemos J, Miljanich G (1998) Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas. Biochemistry 37:15353–15362
Olesen J, Burstein R, Ashina M, Tfelt-Hansen P (2009) Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol 8:679–690
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SMG, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M et al (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–552
Pellerin L, Magistretti PJ (1997) Glutamate uptake stimulates Na+, K+ −ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69:2132–2137
Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83(1):117–161
Pietrobon D (2005a) Function and dysfunction of synaptic calcium channels: insights from mouse models. Curr Opin Neurobiol 15:257–265
Pietrobon D (2005b) Migraine: new molecular mechanisms. Neuroscientist 11:373–386
Pietrobon D (2007) Familial hemiplegic migraine. Neurotherapeutics 4:274–284
Pietrobon D (2010) Cav2.1 channelopathies. Pflugers Arch 460:375–393
Pietrobon D, Striessnig J (2003) Neurobiology of migraine. Nat Rev Neurosci 4:386–398
Pineda JC, Waters RS, Foehring RC (1998) Specificity in the interaction of HVA Ca2+ channel types with Ca2+ dependent AHPs and firing behavior in neocortical pyramidal neurons. J Neurophysiol 79:2522–2534
Plummer MR, Logothetis DE, Hess P (1989) Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons. Neuron 2:1453–1463
Qian J, Noebels JL (2000) Presynaptic Ca2+ influx at a mouse central synapse with Ca2+ channel subunit mutations. J Neurosci 20:163–170
Qian J, Noebels JL (2001) Presynaptic Ca2+ channels and neurotransmitter release at the terminal of a mouse cortical neuron. J Neurosci 21:3721–3728
Riant F, Roze E, Barbance C, Méneret A, Guyant-Maréchal L, Lucas C, Sabouraud P, Trébuchon A, Depienne C, Tournier-Lasserve E (2012) PRRT2 mutations cause hemiplegic migraine. Neurology 79(21):2122–2124
Rose EM et al (2009) Glutamate transporter coupling to Na,KATPase. J Neurosci 29:8143–8155
Rozov A, Burnashev N, Sakmann B, Neher E (2001) Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics. J Physiol 531:807–826
Sabatini BL, Regehr WG (1999) Timing of synaptic transmission. Annu Rev Physiol 61:521–542
Schneggenburger R, Forsythe ID (2006) The calyx of Held. Cell Tissue Res 326:311–337
Schneggenburger R, Neher E (2000) Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406:889–893
Serra SA, Fernandez-Castillo N, Macaya A, Cormand B, Valverde MA, Fernandez-Fernandez JM (2009) The hemiplegic migraineassociated Y1245C mutation in CACNA1A results in a gain of channel function due to its effect on the voltage sensor and Gprotein-mediated inhibition. Pflugers Arch 458:489–502
Somjen GG (2001) Mechanisms of spreading depression and hypoxicspreading depression-like depolarization. Physiol Rev 81:1065–1096
Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinnegger MJ, Glossmann H (1998) Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 19:108–115
Suzuki M, Van Paesschen W, Stalmans I, Horita S et al (2010) Defective membrane expression of the Na+-HCO3- cotransporter NBCe1 is associated with familial migraine. Proc Natl Acad Sci USA 107(36):15963–15968
Takago H, Nakamura Y, Takahashi T (2005) G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held. Proc Natl Acad Sci USA 102:7368–7373
Takahashi T, Forsythe I, Tsujimoto T, Barnes-Davies M, Onodera K (1996) Presynaptic calcium current modulation by a metabotropic glutamate receptor. Science 274:594–597
Thomsen LL, Eriksen MK, Roemer SF, Andersen I, Olesen J, Russell MB (2002) A population-based study of familial hemiplegic migraine suggests revised diagnostic criteria. Brain 125:1379–1391
Thomsen LL, Kirchmann M, Bjornsson A, Stefansson H, Jensen RM, Fasquel AC, Petursson H, Stefansson M, Frigge ML, Kong A, Gulcher J, Stefansson K, Olesen J (2007) The genetic spectrum of a population-based sample of familial hemiplegic migraine. Brain 130:346–356
Tottene A, Volsen S, Pietrobon D (2000) Alpha(1E) subunits form the pore of three cerebellar R-type calcium channels with different pharmacological and permeation properties. J Neurosci 20:171–178
Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, Pietrobon D (2002) Familial hemiplegic migraine mutations increase Ca2+ influx through single human CaV2.1 channels and decrease maximal Cav2.1 current density in neurons. Proc Natl Acad Sci USA 99:13284–13289
Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AMJM, Pietrobon D (2005) Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. J Biol Chem 280:17678–17686
Tottene A, Conti R, Fabbro A, Vecchia D, Shapovalova M, Santello M, van den Maagdenberg AM, Ferrari MD, Pietrobon D (2009) Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in CaV2.1 knock in migraine mice. Neuron 61:762–773 A gain of function of excitatory neurotransmission at pyramidal cell synapses but unaltered inhibitory neurotransmission at fast-spiking interneuron synapses is shown. The synapse-specific effect of FHM1 mutations points to disruption of excitation-inhibition balance and neuronal hyperactivity as the basis for episodic vulnerability to cortical spreading depression ignition in migraine
Tozzia A, de Iurea A, Di Filippoa M, Costaa C, Capronia S, Pisanib A, Bonsib P, Picconib B, Cupinic LM, Materazzid S, Geppettid P, Sarchiellia P, Calabresia P (2012) Critical role of calcitonin gene-related peptide receptors in cortical spreading depression. Proc Natl Acad Sci USA 109(46):18985–18990
Tsujimoto T, Jeromin A, Saitoh N, Roder JC, Takahashi T (2002) Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium currents at presynaptic nerve terminals. Science 295:2276–2279
Uchitel OD, Di Guilmi MN, Urbano FJ, Gonzalez-Inchauspe C (2010) Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels (Austin) 4(6):490–496
Urbano FJ, Piedras-Rentería ES, Jun K, Shin HS, Uchitel OD, Tsien RW (2003) Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels. Proc Natl Acad Sci USA 100:3491–3496
van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Ferrari MD (2004) A Cacna1a knock-in migraine mouse model with increased susceptibility to cortical spreading depression. Neuron 41:701–710
van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD (2007) Migraine: gene mutations and functional consequences. Curr Opin Neurol 20:299–305
van den Maagdenberg AM, Pizzorusso T, Kaja S, Terpolilli N, Shapovalova M, Hoebeek FE, Barrett CF, Gherardini L, van de Ven RC, Todorov B, Broos LA, Tottene A, Gao Z, Fodor M, De Zeeuw CI, Frants RR, Plesnila N, Plomp JJ, Pietrobon D, Ferrari MD (2010) High cortical spreading depression susceptibility and migraine-associated symptoms in Cav2.1 S218L mice. Ann Neurol 67:85–98
Volsen SG, Day NC, McCormack AL, Smith W, Craig PJ, Beattie R, Ince PG, Shaw PJ, Ellis SB, Gillespie A (1995) The expression of neuronal voltage-dependent calcium channels in human cerebellum. Brain Res Mol Brain Res 34:271–282
Von Gersdorff H, Borst JG (2002) Short-term plasticity at the calyx of Held. Neuroscience 3:53–64
Von Gersdorff H, Schneggenburger R, Weis S, Neher E (1997) Presynaptic depression at a calyx synapse: the small contribution of metabotropic glutamate receptors. J Neurosci 17(21):8137–8146
Walter JT, Alviña K, Womack MD, Chevez C, Khodakhah K (2006) Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci 9:389–397
Wang L-Y, Kaczmarek LK (1998) High-frequency firing helps replenish the readily releasable pool of synaptic vesicles. Nature 394:384–388
Weiss N, Sandoval A, Felix R, Van den Maagdenberg A, De Waard M (2008) The S218L familial hemiplegic migraine mutation promotes deinhibition of Ca(v)2.1 calcium channels during direct G-protein regulation. Pflugers Arch 457:315–326
Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TVB, Snutch TP, Catterall WA (1995) Immunochemical identification and subcellular distribution of the a1A subunits of brain calcium channels. J Neurosci 15:6403–6418
Wong AYC, Graham BP, Billups B, Forsythe ID (2003) Distinguishing between presynaptic and postsynaptic mechanisms of short-term depression during action potential trains. J Neurosci 23:4868–4877
Wu LG, Westenbroek RE, Borst JGG, Catterall WA, Sakmann B (1999) Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J Neurosci 19:726–736
Xu W, Lipscombe D (2001) Neuronal CaV1 D.3. Alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci 21:5944–5951
Xu J, Wu LG (2005) The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse. Neuron 46:633–645
Zaitsev AV, Povysheva NV, Lewis DA, Krimer LS (2007) P/Qtype, but not N-type, calcium channels mediate GABA release from fast-spiking interneurons to pyramidal cells in rat prefrontal cortex. J Neurophysiol 97:3567–3573
Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405
Acknowledgments
This work was supported by the following grant: PICT-2011-2667 FONCYT (ANPCyT, Argentina), UBACYT20020100100427 (Argentina) and Wellcome Trust #084636 (UK).
Conflict of interest
There are no conflicts of interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
Special Issue: Advances in Biophysics in Latin America
Rights and permissions
About this article
Cite this article
Uchitel, O.D., González Inchauspe, C. & Di Guilmi, M.N. Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models. Biophys Rev 6, 15–26 (2014). https://doi.org/10.1007/s12551-013-0126-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12551-013-0126-y