Abstract
The striatum is innervated by histaminergic fibers and expresses a high density of histamine H3 receptors (H3Rs), present on medium spiny neurons (MSNs) and corticostriatal afferents. In this study, in sagittal slices from the rat dorsal striatum, excitatory postsynaptic potentials (EPSPs) were recorded in MSNs after electrical stimulation of corticostriatal axons. The effect of H3R activation and blockers of calcium and potassium channels was evaluated with the paired-pulse facilitation protocol. In the presence of the H3R antagonist/inverse agonist clobenpropit (1 μM), the H3R agonist immepip (1 μM) had no effect on the paired-pulse ratio (PPR), but in the absence of clobenpropit, immepip induced a significant increase in PPR, accompanied by a reduction in EPSP amplitude, suggesting presynaptic inhibition. The blockade of CaV2.1 (P/Q-type) channels with ω-agatoxin TK (400 nM) increased PPR and prevented the effect of immepip. The CaV2.2 (N-type) channel blocker ω-conotoxin GVIA (1 μM) also increased PPR, but did not occlude the immepip action. Functional KIR3 channels are present in corticostriatal terminals, and in experiments in which immepip increased PPR, the KIR3 blocker tertiapin-Q (30 nM) prevented the effect of the H3R agonist. These results indicate that the presynaptic modulation by H3Rs of corticostriatal synapses involves the inhibition of Cav2.1 calcium channels and the activation of KIR3 potassium channels.
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Data Availability
Data can be obtained upon request to the corresponding author.
Abbreviations
- D1-MSN:
-
D1 receptor-expressing medium spiny neuron
- D2-MSN:
-
D2 receptor-expressing medium spiny neuron
- EPSP:
-
Excitatory postsynaptic potential
- GIRK:
-
G protein-activated inwardly rectifying potassium channel
- H3R:
-
Histamine H3 receptor;
- MSN:
-
Medium spiny neuron
- PPR:
-
Paired-pulse ratio
References
Alexander SP, Catterall WA, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA, Collaborators C (2015) The concise guide to PHARMACOLOGY 2015/16: voltage-gated ion channels. Br J Pharmacol 172(24):5904–5941. https://doi.org/10.1111/bph.13349
Andreasen M, Hablitz J (1995) Paired-pulse facilitation in the dentate girus: a patch-clamp study in rat hippo-campus in vitro. Neurosci Lett 72:326–336
Arias-Montaño J, Floran FB, Aceves J (2007) Dopamine D1 receptor facilitation of depolarization-induced release of gamma-amino-butyric acid in rat striatum is mediated by the cAMP/PKA pathway and involves P/Q-type calcium channels. Synapse 61:310–319. https://doi.org/10.1002/syn.20372
Arias-Montaño J, Florán B, García M, Aceves J, Young J (2001) Histamine H3 receptor-mediated inhibition of depolarisation-induced, dopamine D1 receptor-dependent release of [3H]-g-aminobutyric acid in rat striatum. Br J Pharmacol 133:165–171
Bai YF, Ma H, Liu LN, Li H, Li XX, Yang YT, Xue B, Wang D, Xu ZQ (2018) Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channel. Biochem Biophys Res Commun 503:79–85. https://doi.org/10.1016/j.bbrc.2018.05.181
Barral J, Galarraga E, Bargas J (1999) Muscarinic presynaptic inhibition of neostriatal glutamatergic afferents is mediated by Q-type Ca2+ channels. Brain Res Bull 49(4):285–289
Barral J, Mendoza E, Galarraga E, Bargas J (2003) The presynaptic modulation of corticostriatal afferents by mu-opioids is mediated by K+ conductances. Eur J Pharmacol 462(1–3):91–98
Barral J, Poblette F, Mendoza E, Pineda JC, Galarraga E, Bargas J (2001) High-affinity inhibition of glutamate release from corticostriatal synapses by omega-agatoxin TK. Eur J Pharmacol 430(2–3):167–173
Barral J, Toro S, Galarraga E, Bargas J (2000) GABAergic presynaptic inhibition of rat neostriatal afferents is mediated by Q-type Ca(2+) channels. Neurosci Lett 283(1):33–36
Barret E, Stevens C (1972) The kinetics of transmitter release at the frog neuromuscular junction. J Physiol 227:691–708
Bolam JP, Ellender TJ (2016) Histamine and the striatum. Neuropharmacology 106:74–84. https://doi.org/10.1016/j.neuropharm.2015.08.013
Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3(8):a003947. https://doi.org/10.1101/cshperspect.a003947
Celanire S, Wijtmans M, Talaga P, Leurs R, de Esch IJ (2005) Keynote review: histamine H3 receptor antagonists reach out for the clinic. Drug Discov Today 10(23–24):1613–1627. https://doi.org/10.1016/S1359-6446(05)03625-1
Charlton M, SJZucker SR (1982) Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse. J Physiol 323:173–193
Dascal N, Kahanovitch U (2015) The roles of gbetagamma and galpha in gating and regulation of GIRK channels. Int Rev Neurobiol 123:27–85. https://doi.org/10.1016/bs.irn.2015.06.001
Dauvilliers Y et al (2019) Long-term use of pitolisant to treat patients with narcolepsy. Harmony III Study. Sleep. https://doi.org/10.1093/sleep/zsz174
Debanne D, Guérineau M, Gähwiler B, Thompson S (1996) Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J Physiol Lond 491:163–176
Doreulee N, Yanovsky Y, Flagmeyer I, Stevens DR, Haas HL, Brown RE (2001) Histamine H(3) receptors depress synaptic transmission in the corticostriatal pathway. Neuropharmacology 40(1):106–113
Dunwiddie T, Hass H (1985) Adenosine increases synaptic facilitation in the in vitro rat hippocampus: evidence for a presynaptic site of action. J Physiol 369:365–377
Ellenbroek BA, Ghiabi B (2014) The other side of the histamine H3 receptor. Trends Neurosci 37(4):191–199. https://doi.org/10.1016/j.tins.2014.02.007
Ellender T, Huerta-Ocampo I, Deisseroth K, Capogna M, Bolam JP (2011) Differential modulation of excitatory and inhibitory striatal synaptic transmission by histamine. J Neurosci 31(43):15340–15351
Garduño-Torres B, Treviño M, Gutiérrez R, Arias-Montaño J (2007) Presynaptic histamine H3 receptors regulate glutamate, but not GABA release in rat thalamus. Neuropharmacology 52:527–535
Gerfen CR, Bolam P (2010) The Neuroanatomical organization of the basal ganglia. In: Steiner H, Tseng KY (eds) Handbook of basal ganglia structure and function. Academic Press, Londres, pp 3–28
Ghamari N, Zarei O, Arias-Montaño JA, Reiner D, Dastmalchi S, Stark H, Hamzeh-Mivehroud M (2019) Histamine H3 receptor antagonists/inverse agonists: where do they go? Pharmacol Ther 200:69–84. https://doi.org/10.1016/j.pharmthera.2019.04.007
Gomez-Ramirez J, Johnston TH, Visanji NP, Fox SH, Brotchie JM (2006) Histamine H3 receptor agonists reduce L-dopa-induced chorea, but not dystonia, in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Mov Disord 21(6):839–846. https://doi.org/10.1002/mds.20828
González-Sepúlveda M, Rosell S, Hoffmann H, Castillo-Ruiz M, Mignon V, Moreno-Delgado D, Vignes M, Díaz J, Sabriá J, Ortiz J (2013) Cellular distribution of the histamine H3 receptor in the basal ganglia: functional modulation of dopamine and glutamate neurotransmission. Basal Ganglia 3:109–121
Hansen KB, Mullasseril P, Dawit S, Kurtkaya NL, Yuan H, Vance KM, Orr AG, Kvist T, Ogden KK, Le P, Vellano KM, Lewis I, Kurtkaya S, Du Y, Qui M, Murphy TJ, Snyder JP, Brauner-Osborne H, Traynelis SF (2010) Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists. J Pharmacol Exp Ther 333(3):650–662. https://doi.org/10.1124/jpet.110.166256
Jang IS, Rhee JS, Watanabe T, Akaike N, Akaike N (2001) Histaminergic modulation of GABAergic transmission in rat ventromedial hypothalamic neurones. J Physiol 534(Pt 3):791–803. https://doi.org/10.1111/j.1469-7793.2001.00791.x
Jiang ZG, North RA (1991) Membrane properties and synaptic responses of rat striatal neurones in vitro. J Physiol 443:533–553
Jin W, Lu Z (1999) Synthesis of a stable form of tertiapin: a high-affinity inhibitor for inward-rectifier K+ channels. Biochemistry 38(43):14286–14293. https://doi.org/10.1021/bi991205r
Jose X, Pineda JC, Rodriguez C, Mendoza E, Galarraga E, Bargas J, Barral J (2007) Delta opioids reduce the neurotransmitter release probability by enhancing transient (KV4) K+-currents in corticostriatal synapses as evaluated by the paired pulse protocol. Neurosci Lett 414(2):150–154
Kamiya H, Zucker R (1994) Residual Ca2+ and short-term plasticity. Nature 371:603–606
Katz B, Miledi R (1967) The release of acetylcholine from nerve endings by graded electrical pulses. Proc R Soc Lond B 167:23–38
Katz B, Miledi R (1970) Further study of the role of calcium in synaptic trans-mission. J Physiol (London) 207:789–801
Kincaid AE, Wilson CJ (1996) Corticostriatal innervation of the patch and matrix in the rat neostriatum. J Comp Neurol 374(4):578–592. https://doi.org/10.1002/(SICI)1096-9861(19961028)374:4<578:AID-CNE7>3.0.CO;2-Z
Kitamura H, Yokoyama M, Akita H, Matsushita K, Kurachi Y, Yamada M (2000) Tertiapin potently and selectively blocks muscarinic K+ channels in rabbit cardiac myocytes. J Pharmacol Exp Ther 293:196–205
Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (2005) International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels. Pharmacol Rev 57(4):509–526. https://doi.org/10.1124/pr.57.4.11
Leurs R, Chazot PL, Shenton FC, Lim HD, de Esch IJ (2009) Molecular and biochemical pharmacology of the histamine H4 receptor. Br J Pharmacol 157(1):14–23. https://doi.org/10.1111/j.1476-5381.2009.00250.x
Luján R, Aguado C (2015) Localization and targeting of GIRK channels in mammalian central neurons. Int Rev Neurobiol 123:161–200
Lüscher C, Slesinger P (2010) Emerging concepts for the G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci 11(5):301–315
Meneses D, Mateos V, Islas G, Barral J (2015) G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation. Synapse 69(9):446–452. https://doi.org/10.1002/syn.21833
Meneses D, Vega AV, Torres-Cruz FM, Barral J (2016) KV1 and KV3 potassium channels identified at presynaptic terminals of the corticostriatal synapses in rat. Neural Plast 2016:8782518. https://doi.org/10.1155/2016/8782518
Miljanich G, Ramachandran J (1995) Antagonist of neural calcium channels: structure, function and thera-peutic implications. Ann Rev Pharmacol Toxicol 35:707–734
Mochida S (2018) Presynaptic calcium channels. Neurosci Res 127:33–44
Molina-Hernandez A, Nunez A, Arias-Montano JA (2000) Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum. NeuroReport 11(1):163–166. https://doi.org/10.1097/00001756-200001170-00032
Molina-Hernández A, Nuñez A, Sierra J, Arias-Montaño J (2001) Histamine H3 receptor activation inhibits glutamate release from rat striatal synaptosomes. Neuropharmacology 41:928–934
Nieto-Alamilla G, Marquez-Gomez R, Garcia-Galvez AM, Morales-Figueroa GE, Arias-Montano JA (2016) The histamine H3 receptor: structure, pharmacology, and function. Mol Pharmacol 90(5):649–673. https://doi.org/10.1124/mol.116.104752
Nisenbaum ES, Wilson CJ (1995) Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons. J Neurosci 15(6):4449–4463
Obeso JA, Lanciego JL (2011) Past, present, and future of the pathophysiological model of the Basal Ganglia. Front Neuroanat 5:39. https://doi.org/10.3389/fnana.2011.00039
Orru M, Bakesova J, Brugarolas M, Quiroz C, Beaumont V, Goldberg SR, Lluis C, Cortes A, Franco R, Casado V, Canela EI, Ferre S (2011) Striatal pre- and postsynaptic profile of adenosine A(2A) receptor antagonists. PLoS ONE 6(1):e16088. https://doi.org/10.1371/journal.pone.0016088
Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL (2015) International union of basic and clinical pharmacology XCVIII histamine receptors. Pharmacol Rev 67(3):601–655. https://doi.org/10.1124/pr.114.010249
Pillot C, Heron A, Cochois V, Tardivel-Lacombe J, Ligneau X, Schwartz JC, Arrang JM (2002) A detailed mapping of the histamine H(3) receptor and its gene transcripts in rat brain. Neuroscience 114(1):173–193
Quiroz C, Lujan R, Uchigashima M, Simoes AP, Lerner TN, Borycz J, Kachroo A, Canas PM, Orru M, Schwarzschild MA, Rosin DL, Kreitzer AC, Cunha RA, Watanabe M, Ferre S (2009) Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway. Sci World J 9:1321–1344. https://doi.org/10.1100/tsw.2009.143
Rausche G, Sarvey J, Heinemann U (1988) Lowering extracellular calcium reverses paired pulse habituation into facilitation in dentate granule cells and removes a late IPSP. Neurosci Lett 88:275–280
Redgrave P, Rodriguez M, Smith Y, Rodriguez-Oroz MC, Lehericy S, Bergman H, Agid Y, DeLong MR, Obeso JA (2010) Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease. Nat Rev Neurosci 11(11):760–772. https://doi.org/10.1038/nrn2915
Robles Gomez AA, Vega AV, Gonzalez-Sandoval C, Barral J (2018) The role of Ca(2+)-dependent K(+)-channels at the rat corticostriatal synapses revealed by paired pulse stimulation. Synapse. https://doi.org/10.1002/syn.22017
Sahlholm K, Nilsson J, Marcellino D, Fuxe K, Arhem P (2007) The human histamine H3 receptor couples to GIRK channels in Xenopus oocytes. Eur J Pharmacol 567(3):206–210. https://doi.org/10.1016/j.ejphar.2007.04.032
Sánchez-Lemus LE, Arias-Montaño JA (2004) Histamine H3 receptor-mediated inhibition of dopamine D1 receptor-induced cAMP formation in rat striatum. Neurosci Lett 364:179–184. https://doi.org/10.1016/j.neulet.2004.04.045
Schneider EH, Seifert R (2016) The histamine H4-receptor and the central and peripheral nervous system: a critical analysis of the literature. Neuropharmacology 106:116–128. https://doi.org/10.1016/j.neuropharm.2015.05.004
Wilson C (2004) Basal Ganglia. In: Sheperd G (ed) The synaptic organization of the brain, 5th edn. Oxford University Pres, New York, pp 361–414
Wu LG, Saggau P (1997) Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 20(5):204–212
Zamponi GW (2015) Calcium channel signaling complexes with receptors and channels. Curr Mol Pharmacol 8(1):8–11
Zucker R (1999) Calcium- and activity-dependent synaptic plasticity. Curr Opin Neurobiol 19:305–313
Zucker RS (1996) Exocitosis: a molecular and physiological perspective. Neuron 17:1049–1055
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The acquisition software in LabViewTM was developed by Jesus Perez Ortega at IFC- UNAM.
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This work was supported by Dirección General de Asuntos del Personal Académico (DGAPA), Universidad Nacional Autónoma de México (UNAM), Grant IN216019 to JB.
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HV-V and CG-S: Investigated, performed, and analyzed all electrophysiological experiments. AVV: Investigation, results discussion, edited the manuscript, and helped to write the manuscript. J-AA-M: Conceived the idea, designed, supervised, and coordinated the project, analyzed the results, and wrote the manuscript. JB: Conceptualization, designed the experiments, methodology, formal analysis, analyzed the results, and wrote the manuscript. JB and J-AA-M contributed equally to this work.
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Vázquez-Vázquez, H., Gonzalez-Sandoval, C., Vega, A.V. et al. Histamine H3 Receptor Activation Modulates Glutamate Release in the Corticostriatal Synapse by Acting at CaV2.1 (P/Q-Type) Calcium Channels and GIRK (KIR3) Potassium Channels. Cell Mol Neurobiol 42, 817–828 (2022). https://doi.org/10.1007/s10571-020-00980-6
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DOI: https://doi.org/10.1007/s10571-020-00980-6