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The glutamatergic nerve terminal

  • Chapter
EJB Reviews 1993

Part of the book series: EJB Reviews ((EJB REVIEWS,volume 1993))

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Abstract

The human brain has about 1010 neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these 1013 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982; Cotman et al., 1988; Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986; Choi, 1988; Meldrum and Garthwaite, 1990).

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Abbreviations

NMDA:

N-methyl D-aspartate

GABA:

4-amino-butyrate

CNS:

central nervous system

KA:

kainite

FCCP:

car-bonylcyanide p-trifluoromethoxyphenylhydrazone

4AP:

4-amino-pyridine

Aga-GI:

Agatoxin, glutamate-release inhibiting

PKC:

protein kinase C

MARCKS:

myrisoylated alanine-rich PKC substrate

GAP-43:

a 57-kDa growth-associated protein

CaM-kinase II:

Ca2+-calmodulin-dependent protein kinase II

G-protein:

GTP-binding protein

References

  • Adams, M. E., Bindokas, V. P., Hasegawa, L. & Venema, V. J. (1990) Omega-agatoxins: novel calcium channel antagonists of two sub-types from funnel web spider (Agelenopsis aperta) venom, J. Biol. Chem. 265, 861–867.

    PubMed  CAS  Google Scholar 

  • Adamson, P., Hajimohammadreza, I., Brammer, M. J., Campbell, I. C. & Meldrum, B. S. (1990) Presynaptic glutamate quisqualate receptors — effects on synaptosomal free calcium concentrations, J. Neurochem. 55, 1850–1850.

    Article  PubMed  CAS  Google Scholar 

  • Adam-Vizi, V. & Ashley, R. H. (1987) Relation of acetylcholine release to Ca2+ uptake and intraterminal Ca2+ in guinea-pig cor-tex synaptosomes, J. Neurochem. 49, 1013–1021.

    Article  PubMed  CAS  Google Scholar 

  • Adam-Vizi, V. & Ligeti, E. (1986) Ca2+ uptake by synaptosomes as a function of membrane potential, J. Physiol. (Lond). 372, 363--377.

    CAS  Google Scholar 

  • Adler, E. M., Augustine, G. J., Duffy, S. N. & Charlton, M. P. (1991) Alien intracellular calcium chelators attenuate neurotransmitter release at the squid giant synapse, J. Neurosci. 11, 1496–1507.

    PubMed  CAS  Google Scholar 

  • Agoston, D. V., Hargittai, R & Nagy, A. (1983) Effects of 4-amino-pyridine in Ca2+ movements and changes of membrane potential in pinched-off nerve terminals from rat cerebral cortex, J. Neuro-chem. 41, 745–751.

    CAS  Google Scholar 

  • Agoston, D. V., Conlon, J. M. & Whittaker, V. R. (1988) Selective depletion of the acetylcholine and vasoactive intestinal polypep-tide of the guinea-pig myenteric plexus by differential mobiliz-ation of distinct transmitter pools, Exp. Brain Res. 72, 535–542.

    Article  PubMed  CAS  Google Scholar 

  • Albert, K. A., Walaas, S. I., Wang, J. K. T. & Greengard, R (1986) Widespread occurrence of 87 kDa, a major specific substrate for protein kinase C, Proc. Natl Acad. Sci. USA 83,2822–2826.

    Article  PubMed  CAS  Google Scholar 

  • Anwyl, R. (1991) The role of the metabotropic receptor in synaptic plasticity, Trends Pharmacol. Sci. 12, 324–326.

    Article  PubMed  CAS  Google Scholar 

  • Ase, K., Saito, N., Shearman, M. S., Kikkawa, U., Ono, Y., Igarashi, K., Tanaka, C. & Nishizuka, Y. (1988) Distinct cellular ex-pression of fit and fII-subspecies of protein kinase C in rat cer-ebellum, J. Neurosci. 8,3850–3856.

    PubMed  CAS  Google Scholar 

  • Ashley, R. H., Brammer, M. J. & Marchbanks, R. (1984) Measure-ment of intrasynaptosomal free calcium by using the fluorescent indicator quin-2, Biochem. J. 219, 149–158.

    PubMed  CAS  Google Scholar 

  • Augustine, G. J. (1990) Regulation of transmitter release at the squid giant synapse by presynaptic delayed rectifier potassium current, J. Physiol. (Lond.) 431, 343–364.

    CAS  Google Scholar 

  • Bahler, M. & Greengard, R. (1987) Synapsin I bundles F-actin in a phosphorylation-dependent manner, Nature 326, 704–707.

    Article  PubMed  CAS  Google Scholar 

  • Barbour, B., Brew, H. & Attwell, D. (1988) Electrogenic glutamate uptake in glial cells is activated by intracellular potassium, Nature 335, 433–435.

    Article  PubMed  CAS  Google Scholar 

  • Barbour, B., Szatkowski, M., Ingledew, N. & Attwell, D. (1989) Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells, Nature 342, 918–920.

    Article  PubMed  CAS  Google Scholar 

  • Barnard, E. (1992) Will the real NMDA receptor please stand up?, Trends. Pharmacol. Sci. 13,11–12.

    Article  PubMed  CAS  Google Scholar 

  • Barrie, A. R & Nicholls, D. G. (1993) Adenosine A, receptor inhi-bition of glutamate exocytosis and protein kinase C-mediated decoupling, J. Neurochem.,in the press.

    Google Scholar 

  • Barrie, A. R, Nicholls, D. G., Sanchez-Prieto, J. & Sihra, T. S. (1991) An ion channel locus for the protein kinase C potentiation of transmitter glutamate release from guinea pig cerebrocortical synaptosomes, J. Neurochem. 57,1398–1404.

    Article  PubMed  CAS  Google Scholar 

  • Bartfai, T., Iverfeldt, K., Fisone, G. & Serfözö, R (1988) Regulation of the release of coexisting neurotransmitters, Annu. Rev. Phar-mac. Toxicol. 28, 285–310.

    Article  CAS  Google Scholar 

  • Bartschat, D. K. & Blaustein, M. P. (1985a) Potassium channels in isolated presynaptic nerve terminals from rat brain, J. Physiol. (Lond.) 361, 419–440.

    CAS  Google Scholar 

  • Bartschat, D. K. & Blaustein, M. P. (1985b) Ca2+- activated K- channelsin nerve terminals from rat brain, J. Physiol. (Lond.) 361,441–457.

    CAS  Google Scholar 

  • Baskys, A. & Malenka, R. C. (1991) Agonists at metabotropic gluta-mate receptors presynaptically inhibit EPSCs in neonatal rat hip-pocampus, J. Physiol. (Lond.) 444,687–701.

    CAS  Google Scholar 

  • Benfenati, E., Valtorta, F. & Greengard, R (1991) Computer mode-ling of synapsin I binding to synaptic vesicles and F-actin: impli-cations for regulation of neurotransmitter release, Proc. Natl Acad. Sci. USA 88, 575–579.

    Article  PubMed  CAS  Google Scholar 

  • Benishin, C. G., Krueger, B. K. & Blaustein, M. P. (1988a) Pheno-thiazines and haloperidol block Ca2+- activated K--channels in rat forebrain synaptosomes, Mol. Pharmacol. 33, 195–201.

    CAS  Google Scholar 

  • Benishin, C. G., Sorensen, R. G., Brown, W. E., Krueger, B. K. & Blaustein, M. P. (1988b) Four polypeptide components of green mamba venom selectively block certain K+ channels in rat brain synaptosomes, Mol. Pharmacol. 340, 152–159.

    Google Scholar 

  • Blaustein, M. P. & Goldring, J. M. (1975) Membrane potential in pinched-off presynaptic nerve terminals monitored with a fluor-escent probe: evidence that synaptosomes have potassium dif-fusion potentials, J. Physiol. (Lond.) 247,589–615.

    CAS  Google Scholar 

  • Blaustein, M. P., Rogowski, R. S., Schneider, M. J. & Krueger, B. K. (1991) Polypeptide toxins from the venoms of Old World and New World scorpions preferentially block different potassium channels, Mol. Pharmacol. 40,932–942.

    PubMed  CAS  Google Scholar 

  • Bliss, T. V. P. & Dolphin, A. C. (1982) What is the mechanism of long-term potentiation in the hippocampus?, Trends. Neurosci. 5, 289–290.

    Article  Google Scholar 

  • Bohme, G. A., Bon, C., Stutzmann, J. M., Doble, A. & Blanchard, J. C. (1991) Possible involvement of nitric oxide in long-term potentiation. Eur. J. Pharmacol. 199, 379–381.

    Article  PubMed  CAS  Google Scholar 

  • Bon, C., Bohme, G. A., Doble, A., Stutzmann, J. M. & Blanchard, J. C. (1992) A role for NO in LTP, Eur. J. Neurosci. 4,420--424.

    Article  PubMed  Google Scholar 

  • Booth, R. F. G. & Clark, J. B. (1978) A rapid method for the prep-aration of relatively pure metabolically active synaptosomes from rat brain, Biochem. J. 176, 365–370.

    PubMed  CAS  Google Scholar 

  • Bowyer, J. E. & Weiner, N. (1990) Ca2+-evoked [3H]dopamine re-lease from synaptosomes is dependent on neuronal type Ca2+ channels and is not mediated by acetylcholine, glutamate or as-partate release, J. Pharm. Exp. Therap. 254, 664–670.

    CAS  Google Scholar 

  • Brammer, M. J., Richmond, S., Xiang, J. Z., Adamson, P., Hajimo-hammadreza, I., Silva, M. A. & Campbell, I. C. (1991) Kainate and quisqualate effects on rat presynaptic cortical receptors are metabotropic and non-additive, Neurosci. Lett. 128, 231–234.

    CAS  Google Scholar 

  • Brew, H. & Attwell, D. (1987) Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells, Nature 327, 707–709.

    Article  PubMed  CAS  Google Scholar 

  • Brown, A. M. & Birnbaumer, L. (1990) Ionic channels and their regulation by G-protein subunits, Annu. Rev. Physiol. 52,197--213.

    Article  PubMed  CAS  Google Scholar 

  • Brown, D. A. (1990) G-proteins and potassium currents in neurons, Annu. Rev. Physiol. 52, 215–242.

    Article  PubMed  CAS  Google Scholar 

  • Buma, P. (1989) Synaptic and non-synaptic release of neuromedia-tors in the central nervous system, Acta Morphol. Neerl.-Scand. 26, 81–113.

    CAS  Google Scholar 

  • Burger, P. M., Mehl, E., Cameron, P. L., Maycox, P. R., Baumert, M., Lottspeich, F., De Camilli, R & Jahn, R. (1989) Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate, Neuron 3, 715–720.

    Article  PubMed  CAS  Google Scholar 

  • Burger, P. M., Hell, J., Mehl, E., Krasel, C., Lottspeich, F. & Jahn, R. (1991) GABA and glycine in synaptic vesicles — storage and transport characteristics, Neuron 7, 287–293.

    Article  PubMed  CAS  Google Scholar 

  • Burnashev, N., Monyer, H., Seeburg, P. H. & Sakmann, B. (1992) Divalent ion permeability of AMPA receptor channels is domi-nated by the edited form of a single subunit, Neuron 8, 189--198.

    Article  PubMed  CAS  Google Scholar 

  • Carlson, M. D. & Ueda, T. (1990) Accumulated glutamate levels in the synaptic vesicle are not maintained in the absence of active transport, Neurosci. Lett. 110,325–330.

    Article  PubMed  CAS  Google Scholar 

  • Carlson, M. D., Kish, R E. & Ueda, T. (1989) Glutamate uptake into synaptic vesicles: competitive inhibition by bromocryptine, J. Neurochem. 53, 1889–1894.

    Article  PubMed  CAS  Google Scholar 

  • Carvalho, C. A. M., Coutinho, O. P. & Carvalho, A. R (1986) Ca2+ channel blockers on Ca2+ translocation across synaptosomal membranes, .1. Neurochem. 47, 1774–1784.

    Article  CAS  Google Scholar 

  • Choi, D. W. (1988) Glutamate neurotoxicity and diseases of the nervous system (Review), Neuron 1,623–634.

    Article  PubMed  CAS  Google Scholar 

  • Christensen, H. & Fonnum, F. (1991) Uptake of glycine, GABA and glutamate by synaptic vesicles isolated from different regions of rat CNS, Neurosci. Lett. 129,217–220.

    Article  PubMed  CAS  Google Scholar 

  • Coffey, E. T., Sihra, T. S. & Nicholls, D. G. (1992) The role of protein kinase C in the regulation of glutamate release from iso-lated nerve terminals, Soc. Neurosci. Abstr. 18, 273–13.

    Google Scholar 

  • Colby, K. A. & Blaustein, M. P. (1988) Inhibition of voltage-gated K+ channels in synaptosomes by sn-1,2,-dioctanoylglycerol an activator of protein kinase C, J. Neurosci. 8, 4685–4692.

    PubMed  CAS  Google Scholar 

  • Collingridge, G. L. & Singer, W. (1990) EEA pharmacology: excit-atory amino acid receptors and synaptic plasticity, Trends Phar-macol. Sci. 11,290–290.

    Article  CAS  Google Scholar 

  • Cotman, C. W., Monaghan, D T. & Ganong, A. H. (1988) Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity, Annu. Rev. Neurosci. 11, 61–80.

    Article  PubMed  CAS  Google Scholar 

  • Coutinho, O. P., Carvalho, C. A. M. & Carvalho, A. P. (1984) Ca2+ uptake related to 1-depolarization and Na+/Ca2+ exchange in sheep synaptosomes, Brain Res. 290, 261–271.

    Article  PubMed  CAS  Google Scholar 

  • Cruz, L. J. & Olivera, B. M. (1986) Calcium channel antagonists. co-conotoxin defines a new high affinity site, J. Biol. Chem. 261, 6230–6233.

    PubMed  CAS  Google Scholar 

  • Danbolt, N. C., Pines, G. & Kanner, B. I. (1990) Purification and reconstitution of the sodium-and potassium-coupled glutamate transport glycoprotein from rat brain, Biochemistry 29, 6734--6734.

    Article  PubMed  CAS  Google Scholar 

  • Daniell, L. C. & Leslie, S. W. (1983) 45Ca uptake into rat whole brain synaptosomes unaltered by dihydropyridine calcium antag-onists, J. Neurochem. 41, 1455–1459.

    Article  PubMed  CAS  Google Scholar 

  • Daniell, L. C. & Leslie, S. W. (1986) Inhibition of fast phase calcium uptake and endogenous norepinephrine release in rat brain region synaptosomes by ethanol, Brain Res. 377, 18–28.

    Article  PubMed  CAS  Google Scholar 

  • De Camilli, P. & Jahn, R. (1990) Pathways to regulated exocytosis in neurons, Annu. Rev. Physiol. 52, 625–645.

    Article  PubMed  Google Scholar 

  • De Camilli, P., Benfenati, F., Valtorta, F. & Greengard, P. (1990) The synapsins, Annu. Rev. Cell Biol. 6, 433–460.

    Article  PubMed  Google Scholar 

  • De La Monte, S. M., Federoff, H. J., Ng, S. C., Grabczyk, E. & Fishman, M. (1989) GAP-43 gene expression during develop-ment: persistence in a distinctive set of neurons in the mature central nervous system, Dev. Brain Res. 46,161–168.

    Article  Google Scholar 

  • De-Graan, P. N. E., Dekker, L. V., Oestreicher, A. B., Van-der-Voorn, L. & Gispen, W. H. (1989) Determination of changes in the phosphorylation state of the neuron-specific protein kinase C substrate B-50 (GAP43) by quantitative immunoprecipitation, J. Neurochem. 52,17–23.

    Article  PubMed  CAS  Google Scholar 

  • DeBelleroche, J. S. & Bradford, H. F. (1977) On the site of origin of transmitter amino acids released by depolarization of nerve terminals in vitro, J. Neurochem. 29,335–343.

    Article  CAS  Google Scholar 

  • DeGraan, P. N. E., Oestreicher, A. B., Dewit, M., Kroef, M., Schrama, L. H. & Gispen, W. H. (1990) Evidence for the binding of calmodulin to endogenous B-50 (GAP-43) in native synapto-somal plasma membranes, J. Neurochem. 55, 2139–2139.

    Article  CAS  Google Scholar 

  • Dekker, L. V., DeGraan, P. N. E., DeWitt, M., Hens, J. J. H. & Gispen, W. H. (1990a) Depolarization-onduced phosphorylation of the protein kinase C substrate B-50 (GAP-43) in rat cortical synaptosomes, J. Neurochem. 54,1645–1652.

    Article  CAS  Google Scholar 

  • Dekker, L. V., De Graan, P. N., Spierenburg, H., De Wit, M., Ver-steeg, D. H., & Gispen, W. H. (1990b) Evidence for a relationship between B-50 (GAP-43) and [3H]noradrenaline release in rat brain synaptosomes, Eur. J. Pharmacol. 188, 113–122.

    Article  CAS  Google Scholar 

  • Diaz-Guerra M. J. M., Sanchez-Prieto J., Bosca L., Pocock J. M., Barrie A. P. & Nicholls D. G. (1988) Phorbol ester translocation of protein kinase C in guinea-pig synaptosomes and the potenti-ation of calcium-dependent glutamate release, Biochim. Biophys. Acta 970, 157–165.

    Article  PubMed  CAS  Google Scholar 

  • Di Virgilio, E, Lew, P. D. & Pozzan, T. (1984) Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ concentrations, Nature 310, 691–693.

    Article  PubMed  Google Scholar 

  • Dolphin, A. C. (1990) G protein modulation of calcium currents in neurons, Annu. Rev. Physiol. 52, 243–255.

    Article  PubMed  CAS  Google Scholar 

  • Dooley, D. J., Lupp, A., Hertting, G. & Osswald, H. (1988) co-Conotoxin GVIA and pharmacological modulation of hippocam-pal noradrenaline release, Eur. J. Pharmacol. 148,261–267.

    Article  PubMed  CAS  Google Scholar 

  • Dunkley, R R., Jarvie, R E., Heath, J. W., Kidd, G. J. E. & Rostas, J. A. P. (1986) A rapid method for isolation of synaptosomes on percoll gradients, Brain Res. 372, 115–129.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, S. M. J. (1988) Multiple calcium channels in synaptosmes: voltage dependence of 1,4-dihydropyridine binding and effects on function, Biochemistry 27, 5275–5281.

    Article  PubMed  CAS  Google Scholar 

  • Egebjerg, J., Bettler, B., Hermans-Borgmeyer, I. & Heinemann, S. F.(1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA, Nature 351, 745–748.

    Article  PubMed  CAS  Google Scholar 

  • Erecinska, M. (1987) The neurotransmitter amino acid transport sys-tems : a fresh outlook on an old problem, Biochem. Pharmacol. 36, 3547–3555.

    Article  PubMed  CAS  Google Scholar 

  • Ferkany, J. W. & Coyle, J. T. (1982) Kainic acid stimulates excit-atory amino acid release at presynaptic receptors, Nature 298,757–759.

    Article  PubMed  CAS  Google Scholar 

  • Ferkany, J. & Coyle, J. T. (1986) Heterogeneity of Na+-dependent excitatory amino acid uptake mechanisms in rat brain, J. Neuro-sci. Res. 16, 491–503.

    Article  CAS  Google Scholar 

  • Feuerstein, G., Dooley, D. J. & Seeger, W. (1990) J. Pharmacol. Exp. Ther. 252, 778–785.

    PubMed  CAS  Google Scholar 

  • Fink, K., Blohm, M., Molderings, G., Bönisch, H. & Göthert, M. (1992) Preferential location of N-methyl-D-aspartate (NMDA) receptors on postsynaptic membranes and on non-noradrenergic nerve terminals of the rat brain cortex, Naunyn-Schmiedebergs Arch. Pharmacol. 345, 633–638.

    Article  PubMed  CAS  Google Scholar 

  • Fischer-Bovenkerk, C., Kish, P. E. & Ueda, T. (1988) ATP-depen-dent glutamate uptake into synaptic vesicles from cerebellar mu-tant mice, J. Neurochem. 51, 1054–1059.

    Article  PubMed  CAS  Google Scholar 

  • Fletcher, E. J., Mewett, K. N., Drew, C. A., Allan, R. D. & Johnston, G. A. R. (1991) Inhibition of high affinity L-glutamic acid uptake into rat cortical synaptosomes by the conformationally restricted analogue of glutamic acid, cis-1-aminocyclobutane-1,3-dicar-boxylic acid, Neurosci. Lett. 121,133–135.

    Article  PubMed  CAS  Google Scholar 

  • Fox, A. P., Nowycky, M. C. & Tsien, R. W. (1987) Kinetics and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones, J. Physiol. (Lond.) 394,149–172.

    CAS  Google Scholar 

  • Fredholm, B. B. (1988) Presynaptic adenosine receptors, ISI Atlas Sci. Pharmacol. 2, 257–260.

    CAS  Google Scholar 

  • Freeman, E. J., Terrian, D. M. & Dorman, R. V. (1990) Presynaptic facilitation of glutamate release from isolated hippocampal mossy fiber nerve endings by arachidonic acid, Neurochem. Res. 15, 743–750.

    Article  PubMed  CAS  Google Scholar 

  • Fykse, E. M. & Fonnum, F. (1989) Regional distribution of y-amino-butyrate and L-glutamate uptake into synaptic vesicles isolated from rat brain, Neurosci. Lett. 99, 300–304.

    Article  PubMed  CAS  Google Scholar 

  • Fykse, E. M. & Fonnum, F. (1991) Transport of y-aminobutyrate and L-glutamate into synaptic vesicles-effect of different in-hibitors on the vesicular uptake of neurotransmitters and on the Mg2+-ATPase, Biochem. J. 276,363–367.

    PubMed  CAS  Google Scholar 

  • Fykse, E. M., Christiansen, H. & Fonnum, F. (1989) Comparison of the properties of y-aminobutyric acid and L-glutamate uptake into synaptic vesicles isolated from rat brain, J. Neurochem. 52, 946–951.

    Article  PubMed  CAS  Google Scholar 

  • Gannon, R. L. & Terrian, D. M. (1989) BOAA selectively enhances L-glutamate release from guinea-pig hippocampal mossy fiber synaptosomes, Neurosci. Lett. 107,289–289.

    Article  PubMed  CAS  Google Scholar 

  • Gannon, R. L. & Terrian, D. M. (1991) U-50,488H inhibits dynor-phin and glutamate release from guinea-pig hippocampal mossy fiber terminals, Brain Res. 548, 242–247.

    Article  PubMed  CAS  Google Scholar 

  • Gannon, R. L. & Terrian, D. M. (1992) x-Opioid agonists inhibit transmitter release from guinea-pig hippocampal mossy fiber sy-naptosomes, Neurochem. Res. 17, 741–747.

    Article  PubMed  CAS  Google Scholar 

  • Gispen, W. H. (1985) Presynaptic localization of B50 phosphopro-tein: the ACTH-sensitive protein kinase substarte involved in brain polyphosphinositide metabolism, Brain Res. 328, 381--385.

    Article  PubMed  CAS  Google Scholar 

  • Gray, E. G. & Whittaker, V. R. (1962) The isolation of nerve endings from brain: an electron microscopic study of the cell fragments derived by homogenisation and centrifugation, J. Anat. 96, 79--87.

    PubMed  CAS  Google Scholar 

  • Greengard, P. (1987) Neuronal phosphoproteins: mediators of signal transduction, Mol. Neurobiol. 1, 82–119.

    Article  Google Scholar 

  • Griffiths, R., Grieve, A., Dunlop, J., Damgaard, I., Fosmark, H. & Schousboe, A. (1989) Inhibition by excitatory sulphur amino ac-ids of the high-affinity L-glutamate transporter in synaptosomes and in primary cultures of cortical astrocytes and cerebellar neu-rons, Neurochem. Res. 14, 333–343.

    Article  PubMed  CAS  Google Scholar 

  • Hartwig, J. H., Thelen, M., Rosen, A., Janmey, P. A., Nairn, A. C. & Aderem, A. (1992) MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin, Nature 356,618–622.

    Article  PubMed  CAS  Google Scholar 

  • Heemskerk, F. M. J., Schrama, L. H., Gianotti, C., Spierenburg, H., Versteeg, D. H. G., de Graan, P. N. E. & Gispen, W. H. (1990) 4-Aminopyridine stimulates B-50 (GAP43) phosphorylation and [3H]noradrenaline release in rat hippocampal slices, J. Neuro-chem. 54, 863–870.

    CAS  Google Scholar 

  • Hell, J. W., Edelmann, L., Hartinger, J. & Jahn, R. (1991) Functional reconstitution of the y-aminobutyric acid transporter from synap-tic vesicles using artificial ion gradients, Biochemistry 30, 11795–11800.

    Google Scholar 

  • Herrero, I., Castro, E., Miras-Portugal, M. T. & Sanchez-Prieto, J. (1991a) Glutamate exocytosis evoked by 4-aminopyridine is in-hibited by free fatty acids released from rat cerebrocortical syn-aptosomes, Neurosci. Lett. 126,41–44.

    Article  CAS  Google Scholar 

  • Herrero, I., Miras-Portugal, M. T. & Sanchez-Prieto, J. (1991b) Inhi-bition of glutamate release by arachidonic acid in rat cerebrocor-tical synaptosomes, J. Neurochem. 57, 718–721.

    Article  CAS  Google Scholar 

  • Herrero, I., Miras-Portugal, M. T. & Sanchez-Prieto, J. (1992a) Posi-tive feedback of glutamate exocytosis by metabotropic presynap-tic receptor stimulation, Nature 360,163–166.

    Article  CAS  Google Scholar 

  • Herrero, I., Miras-Portugal, M. T. & Sanchez-Prieto, J. (1992b) PKC-independent inhibition of glutamate exocytosis by arachi-donic acis in rat cerebrocortical synaptosomes, FEBS Lett. 296, 317–319.

    Article  CAS  Google Scholar 

  • Hillyard, D. R., Monje, V. D., Mintz, I. M., Bean, B. P., Nadasdi, L., Ramachandran, J., Miljanich, G., Azimi-Zoonooz, A., McIn-tosh, J. M., Cruz, L. J., Imperial, J. S. & Olivera, B. M. (1992) A new Conus peptide ligand for mammalian presynaptic Ca2+ channels, Neuron 9, 69–77.

    Article  PubMed  CAS  Google Scholar 

  • Hirokawa, N., Sobue, K., Kanda, K., Harada, A. & Yorifuji, H. (1989) The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1, J. Cell Biol. 108, 111--126.

    Article  PubMed  CAS  Google Scholar 

  • Hochner, B., Parnas, H. & Parnas, I. (1989) Membrane depolariz-ation evokes neurotransmitter release in the absence of calcium entry, Nature 342,433–435.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann, M. & Seifert, W. (1989) Glutamate transport and not glutamate receptor binding is stimulated by gangliosides in a Ca2+-dependent manner in rat brain synaptic plasma membranes, J. Neurochem. 53, 716–716.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann, M., O’Shea, Greenfield, A., Rogers, S. W., & Heinemann, S. F. (1989) Cloning by functional expression of a member of the glutamate receptor family, Nature 343,643–643.

    Article  Google Scholar 

  • Hoss, W. & Labkovsky, B. (1986) Inactivation of depolarization-induced calcium uptake in rat brain synaptosomes, Neurochem. Res. 11, 1361–1372.

    Article  PubMed  CAS  Google Scholar 

  • Hu, G. Y. & Storm, J. F. (1991) Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons, Brain Res. 568, 339–344.

    Article  PubMed  CAS  Google Scholar 

  • Huttner, W. B., Schiebler, W., Greengard, P. & De Camilli, P. (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly puri-fied synaptic vesicle preparation, J. Cell Biol. 96, 1374–1388.

    Article  PubMed  CAS  Google Scholar 

  • Ikeda, M., Nakazawa, T., Abe, K., Kaneko, T. & Yamatsu, K. (1989) Extracellular accumulation of glutamate in the hippocaampus in-duced by ischaemia is not Ca2+ -dependent — in vitro and in vivo evidence, Neurosci. Lett. 96, 202–206.

    Article  PubMed  CAS  Google Scholar 

  • Jones, P. G. & Roberts, P. J. (1990) Ibotenate stimulates glutamate release from guinea pig cerebrocortical synaptosomes: inhibition by L-2-amino-4-phosphonobutyrate (L-AP4), Neurosci. Lett. 111, 228–232.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I. (1983) Bioenergetics of neurotransmitter transport, Biochim. Biophys. Acta 726, 293–316.

    PubMed  CAS  Google Scholar 

  • Katayama, Y., Kawamata, T., Tamura, T., Hovda, D. A., Becker, D. P. & Tsubokawa, T. (1991) Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral isch-ernia in vivo,Brain Res. 558,136–136.

    Article  PubMed  CAS  Google Scholar 

  • Kato, K. & Fukuda, H. (1982) Baclofen: inhibition of release of glutamate and aspartate from synaptosomes, Gen. Pharmacol. 13, 445–448.

    Article  PubMed  CAS  Google Scholar 

  • Kauppinen, R. A. & Nicholls, D. G. (1986) Synaptosomal bioenerg-etics : the role of glycolysis, pyruvate oxidation and responses to hypoglycaemia, Eur. J. Biochem. 158,159–165.

    Article  PubMed  CAS  Google Scholar 

  • Kauppinen, R. A., Sihra, T. S. & Nicholls, D. G. (1986) Divalent cation modulation of the ionic permeability of the synaptosomal plasma membrane, Biochim. Biophys. Acta 860, 178–184.

    Article  PubMed  CAS  Google Scholar 

  • Kauppinen, R. A., McMahon, H. T. & Nicholls, D. G. (1988) Ca2+-dependent and Ca2+-independent glutamate release, energy status and cytosolic free Ca2+ concentration in isolated nerve terminals following metabolic inhibition: possible relevance to hypoglyca-emia and anoxia, Neurosci. 27, 175–182.

    Google Scholar 

  • Kish, P. E., Kim, S. Y. & Ueda, T. (1989a) Ontogeny of glutamate accumulating activity in rat brain synaptic vesicles, Neurosci. Lett. 97, 185–185.

    Article  CAS  Google Scholar 

  • Kish, P. E., Fischer-Bovenkerk, C. & Ueda, T. (1989b) Active trans-port of y-aminobutyric acid and glycine into synaptic vesicles, Proc. Natl Acad. Sci. USA 86,3877–3881.

    Article  CAS  Google Scholar 

  • Klee, C. B. (1988) Interaction of calmodulin with Ca2+ and target proteins, Mol. Aspects Cell. Regul. 5, 35–56.

    Google Scholar 

  • Kreuger, B. K., Forn, J. & Greengard, P. (1977) Depolarisation-induced phosphorylation of specific proteins, mediated by cal-cium ion influx, in rat brain synaptosomes, J. Biol. Chem. 252,2764–2773.

    Google Scholar 

  • Kumar, K. N., Tilakaratne, N., Johnson, P. S., Allen, A. E. & Michaelis, E. K. (1991) Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex, Nature 354, 70–73.

    Article  PubMed  CAS  Google Scholar 

  • Landis, D. M. D., Hall, A. K., Weinstein, L. A. & Reese, T. S. (1988) The organization of cytoplasm at the presynaptic active zone of a central nervous system synapse, Neuron 1, 201–209.

    Article  PubMed  CAS  Google Scholar 

  • Leslie, S. W., Woodward, J. J. & Wilcox, R. E. (1985) Correlation of rates of calcium entry and endogenous dopamine release in mouse striatal synaptosomes, Brain Res. 325, 99–105.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y. & Storm, D. R. (1990) Regulation of free calmodulin levels by neuromodulin: neuron growth and regeneration, Trends Phar-macol. Sci. 11, 107–111.

    Article  CAS  Google Scholar 

  • Llinas, R., McGuiness, T. L., Leonard, C. S., Sugimori, M. & Green-gard, P. (1985) Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse, Proc. Natl Acad. Sci. USA 82,3035–3039.

    Article  PubMed  CAS  Google Scholar 

  • Llinas, R., Sugimori, M., Lin, J. W. & Cherksey, B. (1989a) Block-ing and isolation of a Ca“-channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison, Proc. Natl Acad. Sci. USA 86, 1689–1693.

    Article  CAS  Google Scholar 

  • Lunas, R., Sugimori, M., Lin, J. W., Leopold, P. L. & Brady, S. T. (1989b) ATP-dependent directional movement of rat synaptic vesicles injected into the presynaptic terminal of squid giant syn-apse, Proc. Natl Acad. Sci. USA 86,5656–5660.

    Article  Google Scholar 

  • Llinas R., Sugimori M. & Silver, R. B. (1992) Microdomains of high calcium concentration in a presynaptic terminal, Science 256, 677–679.

    Article  PubMed  CAS  Google Scholar 

  • Lobur, A. T., Kish, P. E. & Ueda, T. (1990) Synaptic vesicular gluta-mate uptake: modulation by a synaptic cytosolic factor, J. Neuro-chem. 54, 1614–1618.

    CAS  Google Scholar 

  • Lovinger, D. M. (1991) Trans-1-aminocyclopentane-1,3-dicar-boxylic acid (tert-ACPD) decreases synaptic excitation in rat stri-atal slices through a presynaptic action, Neurosci. Lett. 129, 17–21.

    Article  PubMed  CAS  Google Scholar 

  • Lundy, P. M., Stauderman, K. A., Goulet, J. C. & Frew, R. (1989) Effect of w-conotoxin GVIA on Ca2+ influx and endogenous acetylcholine release from chicken brain preparations, Neuro-chem. Int. 14, 49–54.

    Article  CAS  Google Scholar 

  • Marchi, M., Bocchieri, P., Garbarino, L. & Raiteri, M. (1989) Mus-carinic inhibition of endogenous glutamate release from rat hip-pocampus synaptosomes, Neurosci. Lett. 96, 229–234.

    Article  PubMed  CAS  Google Scholar 

  • Massieu, L. & Tapia, R. (1988) Relationship of dihydropyridine binding sites with calcium-dependent neurotransmitter release in synaptosomes, J. Neurochern. 51, 1184–1189.

    Article  CAS  Google Scholar 

  • Masu, M., Tanabe, Y., Tsuchida, K., Shigemoto, R. & Nakanishi, S. (1991) Sequence and expression of a metabotropic glutamate receptor, Nature 349, 760–765.

    Article  PubMed  CAS  Google Scholar 

  • Matthew, W. D., Tsavaler, L. & Reichardt, L. F. (1981) Identification of a synaptic vesicle-specific membrane protein with a wide dis-tribution in neuronal and secretory tissue, J. Cell Biol. 91,257--269.

    Article  PubMed  CAS  Google Scholar 

  • Maura, G., Ricchetti, A. & Raiteri, M. (1986) Serotonin inhibits the depolarization-evoked release of endogenous glutamate from rat cerebellar nerve endings, Neurosci. Lett. 67, 218–222.

    Article  PubMed  CAS  Google Scholar 

  • Maura, G., Giardi, A. & Raiteri, M. (1988) Release-regulating D2 dopamine receptors are located on striatal glutamatergic nerve terminals, J. Pharmacol. Exp. Ther. 247, 680–684.

    PubMed  CAS  Google Scholar 

  • Maura, G., Carbone, R., Guido, M., Pestarino, M. & Raiteri, M. (1991) 5HT2 presynaptic receptors mediate inhibition of gluta-mate release from cerebellar mossy fibre terminals, Eur. J. Phar-macol. 202, 185–190.

    Article  CAS  Google Scholar 

  • Maycox, P. R., Deckwerth, T., Hell, J. W. & Jahn, R. (1988) Gluta-mate uptake by brain synaptic vesicles, J. Biol. Chem. 263, 15423–15428.

    PubMed  CAS  Google Scholar 

  • Maycox, R. R., Hell, J. W. & Jahn, R. (1990) Amino acid neuro-transmission: spotlight on synaptic vesicles, Trends Neurosci. 13, 83–87.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, H. T., Barrie, A. R, Lowe, M. & Nicholls, D. G. (1989) Glutamate release from guinea-pig synaptosomes: stimulation by reuptake-induced depolarization, J. Neurochem. 53, 71–79.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, H. T. & Nicholls, D. G. (1990) Glutamine and aspartate loading of synaptosomes : A reevaluation of effects on calcium-dependent excitatory amino acid release, J. Neurochem. 54,373–380.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, H. T., Rosenthal, L., Meldolesi, J. & Nicholls, D. G. (1990) a-Latrotoxin releases both vesicular and cytoplasmic glut-amate from isolated nerve terminals, J. Neurochem. 55, 2039--2047.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, H. T., Foran, R, Dolly, J. O., Verhage, M., Wiegant, V. M. & Nicholls, D. G. (1992) Characterization of the inhibition of glutamate, GABA and [Metlenkephalin exocytosis from syn-aptosomes caused by tetanus and botulinum neurotoxins, J. Biol. Chem. 267, 21338–21343.

    PubMed  CAS  Google Scholar 

  • McMahon, H. T. & Nicholls, D. G. (1991) Transmitter glutamate release from isolated nerve terminals: evidence for biphasic re-lease and triggering by localized Ca2+, J. Neurochem. 56, 8699.

    Article  Google Scholar 

  • Meldolesi, J. (1982) Studies on the a-latrotoxin receptors in rat brain synaptosomes: correlation between toxin binding and stimulation of transmitter release, J. Neurochem. 38, 1559–1569.

    Article  PubMed  CAS  Google Scholar 

  • Meldolesi, J., Scheer, H., Madeddu, L. & Wanke, E. (1986) Mechan-ism of action of a-latrotoxin : the presynaptic stimulatory toxin of the black widow spider, Trends Pharmacol. Sci. 7, 151–155.

    Article  CAS  Google Scholar 

  • Meldrum, B. & Garthwaite, J. (1990) EAA pharmacology: excit-atory amino acid neurotoxicity and neurodegenerative disease (Review), Trends Pharmacol. Sci. 11, 379–387.

    Article  PubMed  CAS  Google Scholar 

  • Mintz, I. M., Venema, V. J., Adams, M. E. & Bean, B. R. (1990) The funnel-web spider toxin co-AGA-IIIA blocks N- and L-type calcium channels in neurons and cardiac muscle, Soc. Neurosci. Abstr. 1, 956–956.

    Google Scholar 

  • Mintz, I. M., Venema, V. J., Swiderek, K. M., Lee, T. D., Bean, B. R. & Adams, M. E. (1992a) P-type calcium channels blocked by the spider toxin co-Aga-IVA, Nature 355, 827–829.

    Article  CAS  Google Scholar 

  • Mintz, I. M., Adams, M. E. & Bean, B. P. (1992b) P-type calcium channels in rat central and peripheral neurons, Neuron 9, 8598.

    Article  CAS  Google Scholar 

  • Monyer, H., Seeburg, P. H. & Wisden, W. (1991) Glutamate-oper-ated channels — developmentally early and mature forms arise by alternative splicing, Neuron 6, 799–810.

    Article  PubMed  CAS  Google Scholar 

  • Moriyoshi, K., Ishii, T., Shigemoto, R., Mizunu, N. & Nakanishi, S. (1991) Molecular cloning and characterization of the rat NMDA receptor, Nature 354, 31–37.

    Article  PubMed  CAS  Google Scholar 

  • Muniz, Z. M., Tibbs, G. R., Maschot, P., Bougis, P., Nicholls, D. G. & Dolly, J. O. (1990) Homologues of a K+ channel blocker a-dendrotoxin: characterization of synaptosomal binding sites and their coupling to elevation of cytosolic free calcium concen-tration, Neurochem. Int. 16,105–112.

    Article  PubMed  CAS  Google Scholar 

  • Nachshen, D. A. (1985a) Regulation of cytosolic Ca2+ concentration in presynaptic nerve endings isolated from rat brain, J. Physiol. (Lond.) 363, 87–101.

    CAS  Google Scholar 

  • Nachshen, D. A. (1985b) The early time course of K+- stimulated Ca2+ uptake in presynaptic nerve teminals isolated from rat brain, J. Physiol. (Lond.) 361, 251–268.

    CAS  Google Scholar 

  • Nachshen, D. A. & Blaustein, M. P. (1979) Effects of some organic calcium antagonists on calcium influx in presynaptic nerve ter-minals, Mol. Pharmacol. 16, 579–586.

    CAS  Google Scholar 

  • Nachshen, D. A. & Blaustein, M. P. (1980) Some properties of K+- stimulated Cat2+ influx in presynaptic nerve endings, J. Gen. Phy-siol. 76, 709–728.

    Article  CAS  Google Scholar 

  • Nachshen, D. A. & Blaustein, M. P. (1982) Influx of calcium, stron-tium and barium in presynaptic nerve endings, J. Gen. Physiol. 79, 1065–1088.

    Article  PubMed  CAS  Google Scholar 

  • Naito, S. & Ueda, T. (1983) ATP-dependent uptake of glutamate into protein-1 associated synaptic vesicles, J. Biol. Chem. 258, 696–699.

    PubMed  CAS  Google Scholar 

  • Naito, S. & Ueda, T. (1985) Characterization of glutamate uptake into synaptic vesicles, J. Neurochem. 44, 99–109.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi, N., Shneider, N. A. & Axel, R. (1990) A family of gluta-mate receptor genes — evidence for the formation of heteromul-timeric receptors with distinct channel properties, Neuron 5, 569–581.

    Article  PubMed  CAS  Google Scholar 

  • Nelson, N. (1991) Structure, molecular genetics and evolution of vacuolar H--ATPases, J. Bioenerg. Biomembr. 21, 553–571.

    Article  Google Scholar 

  • Nicholls, D. G. (1992) A retrograde step forward?, Nature 360, 106–107.

    Article  PubMed  CAS  Google Scholar 

  • Nicholls, D. G. & Sihra, T. S. (1986) Synaptosomes possess an exocytotic pool of glutamate, Nature 321, 772–773.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, R. A. & Sihra, T. S. (1989) Concentration-dependence of the effect of barium on endogenous glutamate release from rat brain synaptosomes, Soc. Neurosci. Abstr. 15, 474.

    Google Scholar 

  • Nicholls, D. G., Sihra, T. S. & Sanchez-Prieto, J. (1987) Calcium-.dependent and -independent release of glutamate from synapto-somes monitored by continuous fluorometry, J. Neurochem. 49,50–57.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, R. A., Sihra, T. S., Czemik, A. J., Nairn, A. C. & Green-gard, P. (1990) Cat+/calmodulin-dependent protein kinase II in-creases glutamate and noradrenaline release from synaptosomes, Nature 343, 647–650.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, R. A., Chilcote, T. J., Czernik, A. J. & Greengard, P. (1992) Synapsin I regulates glutamate release from rat brain synapto-somes, J. Neurochem. 58,783–785.

    Article  PubMed  CAS  Google Scholar 

  • Oda, T., Shearman, M. S. & Nishizuka, Y. (1991) Synaptosomal protein kinase-C subspecies. B. Down-regulation promoted by phorbol ester and its effect on evoked norepinephrine release, J. Neurochem. 56, 1263–1269.

    Article  PubMed  CAS  Google Scholar 

  • O’Dell, T. J., Hawkins, R. D., Kandel, E. R. & Arancio, O. (1991) Tests of the roles of two diffusible substances in long-term po-tentiation: evidence for nitric oxide as a possible early retrograde messenger, Proc. Natl Acad. Sci. USA 88, 11285–11289.

    Google Scholar 

  • Ogata, T., Nakamura, Y., Shibata, T. & Kataoka, K. (1992) Release of excitatory amino acids from cultured hippocampal astrocytes induced by a hypoxic-hypoglycemic stimulation, J. Neurochem. 58, 1957–1959.

    Article  PubMed  CAS  Google Scholar 

  • Pan-Hou, H., Suda, Y., Sumi, M., Yoshioka, N. & Kawai, N. (1989) A spider toxin (JSTX) inhibits L-glutamate uptake by rat brain synaptosomes, Brain Res. 476,354–357.

    Article  PubMed  CAS  Google Scholar 

  • Parnas, I. & Pamas, H. (1988) The ‘Ca2+-voltage’ hypothesis for neurotransmitter release, Biophys. Chem. 29, 85–93.

    Article  PubMed  CAS  Google Scholar 

  • Petrenko, A. G., Perin, M. S., Davletov, B. A., Ushkaryov, Y. A., Geppert, M. & Sudhof, T. C. (1991) Binding of synaptotagmin to the a-latrotoxin receptor implicates both in synaptic vesicle exocytosis, Nature 353, 65–68.

    Article  PubMed  CAS  Google Scholar 

  • Pittaluga, A. & Raiteri, M. (1992) N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal nor-epinephrine release. I. Location on axon terminals and pharma-cological characterization, J. Pharmacol. Exp. Ther. 260, 232–237.

    PubMed  CAS  Google Scholar 

  • Pocock, J. M. & Nicholls, D. G. (1992) A toxin (Aga-GI) from the venom of the spider Agelenopsis aperta inhibits the mammalian presynaptic Ca2+ channel coupled to glutamate exocytosis, Eur. J. Pharmacol. 226, 343–350.

    Article  PubMed  CAS  Google Scholar 

  • Pocock, J. M., Murphie, H. M. & Nicholls, D. G. (1988) Kainic acid inhibits the synaptosomal plasma membrane glutamate carrier and allows glutamate leakage from the cytoplasm but does not affect glutamate exocytosis, J. Neurochem. 50, 745–751.

    Article  PubMed  CAS  Google Scholar 

  • Pocock, J. M., Venema, V. J. & Adams, M. E. (1992) w-Agatoxins differentially block Ca’ channels in locust, chick and rat synap-tosomes, Neurochem. Int. 20, 263–270.

    Article  PubMed  CAS  Google Scholar 

  • Poli, A., Lucchi, R., Vibio, M. & Barnabei, O. (1991) Adenosine and glutamate modulate each other’s release from rat hippocampal synaptosomes, J. Neurochem. 57, 298–306.

    Article  PubMed  CAS  Google Scholar 

  • Raiteri, M., Garrone, B. & Pittaluga, A. (1992) N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. H. Evidence for functional cooperation and for coexistence on the same axon terminal, J. Pharmacol. Exp. Ther. 260,238–242.

    PubMed  CAS  Google Scholar 

  • Reynolds, I. J., Wagner, J. A., Snyder, S. H., Thayer, S. A., Olivera, B. M. & Miller, R. J. (1986) Brain voltage-sensitive Ca2+ chan-nel subtypes differentiated by w-conotoxin fraction GVIA, Proc. Natl Acad. Sci. USA 83, 8804–8807.

    Article  PubMed  CAS  Google Scholar 

  • Rink, T. J., Sanchez, A. & Hallam, T. J. (1983) DAG and phorbol ester stimulate secretion without raising cytoplasmic free Ca2+ in human platelets, Nature 305, 317–319.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, P. J. & Dunkley, P. R. (1983) Depolarization-dependent protein phosphorylation in rat cortical synaptosomes : the effects of calcium, strontium and barium, Neurosci. Lett. 43, 85–90.

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal, L. & Meldolesi, J. (1989) a-Latrotoxin and related toxins, Pharmacol. Ther. 42, 115–134.

    Article  PubMed  CAS  Google Scholar 

  • Rothman, S. M. & Olney, J. W. (1986) Glutamate and the pathophy-siology of hypoxic-ischaemic brain damage, Ann. Neurol. 19, 105–111.

    Article  PubMed  CAS  Google Scholar 

  • Rubio, I., Tones, M., Miras-Portugal, M. T. & Sanchez-Prieto, J. (1991) Ca2+-independent release of glutamate during in vitro an-oxia in isolated nerve terminals, J. Neurochem. 57, 1159–1162.

    Article  PubMed  CAS  Google Scholar 

  • Sakmann, B. (1992) Elementary steps in synaptic transmission re-vealed by currents through single ion channels, Neuron 8,613--629.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Prieto, J. & Gonzalez, P. (1988) Occurrence of a large Ca2+-independent release of glutamate during anoxia in isolated nerve terminals, J. Neurochem. 50,1322–1324.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Prieto, J., Sihra, T. S. & Nicholls, D. G. (1987a) Charac-terization of the exocytotic release of glutamate from guinea-pig cerebral cortical synaptosomes, J. Neurochem. 49, 58–64.

    Article  CAS  Google Scholar 

  • Sanchez-Prieto, J., Sihra, T. S., Evans, D., Ashton, A., Dolly, J. O. & Nicholls, D. G. (1987b) Botulinum toxin A blocks glutamate exocytosis from guinea-pig cerebral cortical synaptosomes, Eur. J. Biochem. 165, 675–681.

    Article  CAS  Google Scholar 

  • Sandberg, M., Butcher, S. P. & Hagberg, H. (1986) In vivo glutamate efflux in anoxiaJ. Neurochem. 47, 178–184.

    Article  PubMed  CAS  Google Scholar 

  • Scheer, H. W. (1990) Interactions between the presynaptically active neurotoxins alpha-latrotoxin and omega-conotoxin GVIA: stud-ies on calcium fluxes and binding parameters in rat and chicken synaptosomes, Can. J. Physiol. Pharmacol. 68, 1049–1054.

    Article  PubMed  CAS  Google Scholar 

  • Schiavo, G., Poulain, B., Rossetto, O., Benfenati, F., Tauc, L. & Montecucco, C. (1992a) Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity de-pend on zinc, EMBO J. 11,3577–3583.

    CAS  Google Scholar 

  • Schiavo, G., Benfenati, F., Poulain, B., Rossetto, O., Polverino-de-Laureto, P., Dasgupta, B. R. & Montecucco, C. (1992b) Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin, Nature 359, 832–835.

    Article  CAS  Google Scholar 

  • Schiebler, W., Jahn, R., Doucet, J.-P., Rothlein, J. & Greengard, P. (1986) Characterisation of synapsin I binding to small synaptic vesicles, J. Biol. Chem. 261, 8383–8390.

    PubMed  CAS  Google Scholar 

  • Schoepp, D., Bockaert, J. & Sladeczek, F. (1990) Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors (Review), Trends Pharmacol. Sci. 11, 508–508.

    Article  PubMed  CAS  Google Scholar 

  • Schultz, G., Rosenthal, W., Hescheler, J. & Trautwein, W. (1990) Role of G proteins in calcium channel modulation, Annu. Rev. Physiol. 52, 275–292.

    Article  PubMed  CAS  Google Scholar 

  • Scott, I. D. & Nicholls, D. G. (1980) Energy transduction in intact synaptosomes: influence of plasma-membrane depolarization on the respiration and membrane potential of internal mitochondria determined in situ, Biochem. J. 186, 21–33.

    PubMed  CAS  Google Scholar 

  • Scott, I. D., Akerman, K. E. O. & Nicholls, D. G. (1980) Ca2+ transport by intact synaptosomes: intra-synaptosomal compart-mentation and the role of the mitochondrial membrane potential, Biochem. J. 192, 873–880.

    PubMed  CAS  Google Scholar 

  • Shearman, M. S., Shinomura, T., Oda, T. & Nishizuka, Y. (1991) Synaptosomal protein kinase-C subspecies. A. Dynamic changes in the hippocampus and cerebellar cortex concomitant with syn-aptogenesis, J. Neurochem. 56, 1255–1262.

    Article  PubMed  CAS  Google Scholar 

  • Sherman, A. D., Hegwood, T. S., Baruah, S. & Waziri, R. (1992) Presynaptic modulation of amino acid release from synapto-somes, Neurochem. Res. 17, 125–128.

    Article  PubMed  CAS  Google Scholar 

  • Shioi, J., Naito, S. & Ueda, T. (1989) Glutamate uptake into synaptic vesicles of bovine cerebral cortex and electrochemical difference of protons across the membrane, Biochem. J. 258, 499–504.

    PubMed  CAS  Google Scholar 

  • Shioi, J. & Ueda, T. (1990) Artificially imposed electrical potentials drive L-glutamate uptake into synaptic vesicles of bovine cer-ebral cortex, Biochem. I. 267, 63–68.

    CAS  Google Scholar 

  • Sihra T. S. & Nicholls D. G. (1987) 4-Aminobutyrate can be re-leased exocytotically from guinea-pig cerebral cortical synapto-somes. J. Neurochem. 49, 261–267.

    Article  PubMed  CAS  Google Scholar 

  • Simon, S. M. & Llinas, R. (1985) Compartmentalization of the sub-membrane calcium activity during Ca2+ influx and its signfic-ance in transmitter release, Biophys. J. 48, 485–498.

    Article  PubMed  CAS  Google Scholar 

  • Simonato, M., Jope, R. S., Bianchi, C. & Beani, L. (1989) Lack of excitatory amino acid induced effects on Ca2+ fluxes measured with 45Ca2+ in rat cerebral cortex synaptosomes, Neurochem. Res. 14, 677–682.

    Article  PubMed  CAS  Google Scholar 

  • Simpson, L. L. (1989) Botulinum neurotoxin and tetanus toxin,Aca-demic Press, San Diego.

    Google Scholar 

  • Simpson, R. E., O’Regan, M. H., Perkins, L. M. & Phillis, J W. (1992) Excitatory transmitter amino acid release from the isch-emic rat cerebral cortex: effects of adenosine receptor agonists and antagonists, J. Neurochem. 58, 1683–1690.

    Article  PubMed  CAS  Google Scholar 

  • Skene, J. H. P. & Virag, I. (1989) Posttranslational membrane attach-ment and dynamic fatty acylation of neuronal growth cone pro-tein GAP-43, J. Cell Biol. 108, 613–624.

    Article  PubMed  CAS  Google Scholar 

  • Sladeczek F., Pin J. P., Recasens M., Bockaert J. & Weiss S. (1985) Glutamate stimulates inositol phosphate formation in striatal neurones, Nature 317, 717–719.

    Article  PubMed  CAS  Google Scholar 

  • Smith, S. J. & Augustine, G. J. (1988) Calcium ions, active zones and synaptic transmitter release, Trends Neurosci. 11, 458–464.

    Article  PubMed  CAS  Google Scholar 

  • Sudhof, T. C. & Jahn, R. (1991) Proteins of synaptic vesicles in-volved in exocytosis and membrane recycling, Neuron 6, 665--677.

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama, H., Ito I. & Hirono C. (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism, Nature 325,531–533.

    Article  PubMed  CAS  Google Scholar 

  • Suszkiw, J. B. & O’Leary, M. E. (1983) Temporal characteristics of potassium-stimulated acetylcholine release and inactivation of calcium influx in rat brain synaptosomes, .J. Neurochem. 41, 868–873.

    Article  PubMed  CAS  Google Scholar 

  • Suszkiw, J. B., O’Leary, M. E., Murawsky, M. M. & Wang, T. (1986) Presynaptic calcium channels in rat cortical synapto-somes: fast kinetics of phasic calcium influx, channel inacti-vation and relationship to nitrendipine receptors, J. Neurosci. 6, 1349–1357.

    PubMed  CAS  Google Scholar 

  • Suszkiw, J. B., Murawsky, M. M. & Fortner, R. C. (1987) Hetero-geneity of presynaptic Ca2+ channels revealed by species differ-ences in the sensitivity of synaptosomal Ca2+ entry to w-con-otoxin, Biochem. Biophys. Res. Commun. 145, 1283–1286.

    Article  PubMed  CAS  Google Scholar 

  • Suszkiw, J. B., Murawsky, M. M. & Shi, Y. (1989) Further charac-terization of phasic calcium influx in rat cerebrocortical synaptosomes: inferences regarding calcium channel types in nerve end-ings, J. Neurochem. 52, 1260–1269.

    Article  PubMed  CAS  Google Scholar 

  • Tanabe, Y., Masu, M., Ishii, T., Shigemoto, R. & Nakanishi, S. (1992) A family of metabotropic glutamate receptors, Neuron 8, 169–179.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, S., Tominaga, M., Yasuda, I., Kishimoto, A. & Nishizuka, Y. (1991) Protein kinase C in rat brain synaptosomes: flI-sub-species as a major isofonn associated with membrane-skeleton elements, FEBS Lett. 294, 267–270.

    Article  PubMed  CAS  Google Scholar 

  • Terrian, D. M., Hernandez, P. G., Rea, M. A. & Peters, R. I. (1989) ATP release, adenosine formation, and modulation of dynorphin and glutamic acid release by adenosine analogues in rat hippo-campal mossy fibre synaptosomes, .J. Neurochem. 53, 1390--1399.

    Article  PubMed  CAS  Google Scholar 

  • Thomsen, C., Kristensen, P., Mulvihill, E., Haldeman, B. & Suzdak, P. D. (1992) L-AP4 is an agonist at the type IV metabotropic glutamate receptor which is negatively coupled to adenylyl cy-clase, Eur. J. Pharmacol. Mol. Pharmacol. 227, 361–362.

    Article  CAS  Google Scholar 

  • Tibbs, G. R., Barrie, A. P., Van-Mieghem, F., McMahon, H. T. & Nicholls, D. G. (1989a) Repetitive action potentials in isolated nerve terminals in the presence of 4-aminopyridine: effects on cytosolic free Ca2+ and glutamate release, J. Neurochem. 53, 1693–1699.

    Article  CAS  Google Scholar 

  • Tibbs, G. R., Dolly, J. O. & Nicholls, D. G. (1989b) Dendrotoxin, 4-aminopyridine, and ß-bungarotoxin act at common loci but by two distinct mechanisms to induce Ca2+-dependent release of glutamate from guinea-pig cerebrocortical synaptosomes, J. Neu-rochem. 52, 201–206.

    CAS  Google Scholar 

  • Tibbs, G. R., Nicholls, D. G. & Dolly, J. O. (1989c) Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca2+ in cerebrocortical synaptosomes an effect not shared by apamin, FEBS Lett. 255, 159–162.

    Article  CAS  Google Scholar 

  • Tsien, R. Y. (1989) Fluorescent probes of cell signalling, Annu. Rev. Neurosci. 12, 227–253.

    Article  PubMed  CAS  Google Scholar 

  • Turner, T. J. & Goldin, S. M. (1985) Calcium channels in rat brain synaptosomes : identification and pharmacological characteriza-tion. High affinity blockade by organic Ca2+ channel blockers, J. Neurosci. 5, 841–849.

    PubMed  CAS  Google Scholar 

  • Turner, T. J., Pearce, L. B. & Goldin, S. M. (1989) A superfusion system designed to measure release of radiolabeled neuro-transmitter on a subsecond timescale, Anal. Biochem. 178, 8–16.

    Article  PubMed  CAS  Google Scholar 

  • Turner, T. J., Adams, M. E. & Dunlap, K. (1992) Calcium channels coupled to glutamate release identified by co-Aga-IVA, Science 258, 310–313.

    Article  PubMed  CAS  Google Scholar 

  • Uchitel, O. D., Protti, D. A., Sanchez, V., Cherksey, B. D., Sugimori, M. & Llinâs, R. (1992) P-type voltage-dependent calcium chan-nel mediates presynaptic calcium influx and transmitter release in mammalian synapses, Proc. Natl. Acad. Sci. USA 89, 3330–3333.

    Article  PubMed  CAS  Google Scholar 

  • Venema, V. J. & Adams, M. E. (1990) New w-agatoxin calcium channel antagonists from funnel web spider venom active in the avian and mammalian brain, Soc. Neurosci. Abstr. 1, 956–956.

    Google Scholar 

  • Venema, V. J., Swiderek, K. M., Lee, T. D., Hathaway, G. M. & Adams, M. E. (1992) Antagonism of synaptosomal calcium channels by subtypes of w-agatoxins, J. Biol. Chem. 267, 2610--2615.

    PubMed  CAS  Google Scholar 

  • Verhage, M., Besselsen, E., Lopes da Silva, F. H. & Ghijsen, W. E. J. M. (1988) Evaluation of the Ca2+ concentration in purified nerve terminals: relationship between Ca2+ homeostasis and syn-aptosomal preparation, J. Neurochem. 51, 1667–1674.

    Article  PubMed  CAS  Google Scholar 

  • Verhage, M., McMahon, H. T., Ghijsen, W. E. J. M., Boomsma, F., Wiegant, V. & Nicholls, D. G. (1991) Differential release of am-ino acids, neuropeptides and catecholamines from nerve ter-minals, Neuron 6, 517–524.

    Article  PubMed  CAS  Google Scholar 

  • Wang, J. K. T., Walaas, S. I., Sihra, T. S., Aderem, A. & Greengard, R (1989) Phosphorylation and associated translocation of the 87 kDa protein, a major protein kinase C substrate in isolated nerve terminals, Proc. Natl Acad. Sci. USA 86, 2253–2256.

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson, R. & Nicholls, D. G. (1989) Compartmentation of gluta-mate and aspartate within cerebral cortical synaptosomes: evi-dence for a non-cytoplasmic origin for the Ca’ releasable pool of glutamate, Neurochem. Int. 15, 191–197.

    Article  PubMed  CAS  Google Scholar 

  • Williams, J. H., Errington, M. L., Lynch, M. A. & Bliss, T. V. P. (1989) Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus, Nat-ure 341, 739–739.

    Article  CAS  Google Scholar 

  • Woodward, J. J., Cook, M. E. & Leslie, S. W, (1988a) Characteriza-tion of dihydropyridine-sensitive calcium channels in rat brain synaptosomes, Proc. Natl Acad. Sci. USA 85, 7389–7393.

    Article  CAS  Google Scholar 

  • Woodward, J. J., Rezazadeh, S. M. & Leslie, S. W. (1988b) Differen-tial sensitivity of synaptosomal Ca2+ entry and endogenous dopa-mine release to co-conotoxin, Brain Res. 475, 141–145.

    Article  CAS  Google Scholar 

  • Zhu, P. C., Thureson-Klein, A. & Klein, R. L. (1986) Exocytosis from large dense cored vesicles outside the active synaptic zones of terminals within the trigeminal subnucleus caudalis: a possi-ble mechanism for neuropeptide release, Neuroscience 19, 43–54.

    Article  PubMed  CAS  Google Scholar 

  • Zucker, R. S. & Stockbridge, N. (1983) Presynaptic calcium dif-fusion and the time courses of transmitter release and synaptic facilitation at the squid giant synapse, J. Neurosci. 3, 1263--1269.

    PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, University of Dundee, Scotland, DD1 4HN

    David G. Nicholls

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© 1994 Federation of European Biochemical Societies

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Nicholls, D.G. (1994). The glutamatergic nerve terminal. In: EJB Reviews 1993. EJB Reviews, vol 1993. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78757-7_6

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  • DOI: https://doi.org/10.1007/978-3-642-78757-7_6

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