Excitable Astrocytes: Ca2+- and cAMP-Regulated Exocytosis

Neurochemical Research

Volumn 40, Issue 12, 2015, Pages 2414-2424

  Vardjan, Nina ^a,b   Zorec, Robert ^a,b  

^a Celica Biomedical Sciences Center   (Slovenia)

^b UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

cAMP; Cytosolic Ca2+; Regulated exocytosis; Tonic and phasic signalling

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM ION; CYCLIC AMP; G PROTEIN COUPLED RECEPTOR; GLUTAMIC ACID; NEUROPEPTIDE; SNARE PROTEIN;

ARTICLE; ASTROCYTE; EXOCYTOSIS; HOMEOSTASIS; HUMAN; MEMBRANE CHANNEL; MEMBRANE VESICLE; NERVE EXCITABILITY; NEUROSECRETORY CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SECRETION; SIGNAL PROCESSING; ANIMAL; CALCIUM SIGNALING; CYTOSOL; GLIA; METABOLISM; PHYSIOLOGY;

ANIMALS; ASTROCYTES; CALCIUM SIGNALING; CYCLIC AMP; CYTOSOL; EXOCYTOSIS; HUMANS; NEUROGLIA;

EID: 84949316264     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-015-1545-x     Document Type: Article

References (131)

1. 2+ master key. Neuroscientist 17:513–523
2. Verkhratsky A, Orkand RK, Kettenmann H (1998) Glial calcium: homeostasis and signaling function. Physiol Rev 78:99–141
3. Fujita T, Chen MJ, Li B, Smith NA, Peng W, Sun W, Toner MJ, Kress BT, Wang L, Benraiss A et al (2014) Neuronal transgene expression in dominant-negative SNARE mice. J Neurosci 34:16594–16604
4. Sloan SA, Barres BA (2014) Looks can be deceiving: reconsidering the evidence for gliotransmission. Neuron 84:1112–1115
5. Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999) Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22:208–215
6. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431
7. Vardjan N, Kreft M, Zorec R (2014) Regulated exocytosis in astrocytes is as slow as the metabolic availability of gliotransmitters: focus on glutamate and ATP. Adv Neurobiol 11:81–101
8. Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, Jacob Filho W, Lent R, Herculano-Houzel S (2009) Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol 513:532–541
9. Haydon PG (2001) GLIA: listening and talking to the synapse. Nat Rev Neurosci 2:185–193
10. Vesce S, Bezzi P, Volterra A (1999) The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 56:991–1000
11. 2+ as a signalling route. ASN Neuro 4:106–119
12. Gabrielli M, Battista N, Riganti L, Prada I, Antonucci F, Cantone L, Matteoli M, Maccarrone M, Verderio C (2015) Active endocannabinoids are secreted on extracellular membrane vesicles. EMBO Rep 16:213–220
13. Kirov SA, Sorra KE, Harris KM (1999) Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats. J Neurosci 19:2876–2886
14. Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192
15. Oberheim NA, Wang X, Goldman S, Nedergaard M (2006) Astrocytic complexity distinguishes the human brain. Trends Neurosci 29:547–553
16. Han X, Chen M, Wang F, Windrem M, Wang S, Shanz S, Xu Q, Oberheim NA, Bekar L, Betstadt S et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–353
17. Benarroch EE (2009) The locus ceruleus norepinephrine system: functional organization and potential clinical significance. Neurology 73:1699–1704
18. Araque A, Parpura V, Sanzgiri RP, Haydon PG (1998) Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur J Neurosci 10:2129–2142
19. 2+-dependent exocytosis in cultured astrocytes. Glia 46:437–445
20. Kettenmann H, Faissner A, Trotter J (1996) Neuron-glia interactions in homeostasis and degeneration. In: Greger R, Windhorst U (eds) Comprehensive human physiology. Springer, Berlin, pp 533–543
21. Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhäuser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7:613–620
22. Hamilton NB, Attwell D (2010) Do astrocytes really exocytose neurotransmitters? Nat Rev Neurosci 11:227–238
23. Li D, Hérault K, Silm K, Evrard A, Wojcik S, Oheim M, Herzog E, Ropert N (2013) Lack of evidence for vesicular glutamate transporter expression in mouse astrocytes. J Neurosci 33:4434–4455
24. 2+ -regulated exocytosis from cortical astrocytes. J Neurosci 28:7648–7658
25. Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52(1–2):142–154
26. Woo DH, Han KS, Shim JW, Yoon BE, Kim E, Bae JY, Oh SJ, Hwang EM, Marmorstein AD, Bae YC et al (2012) TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151:25–40
27. Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD (2008) What is the role of astrocyte calcium in neurophysiology? Neuron 59:932–946
28. Guček A, Vardjan N, Zorec R (2012) Exocytosis in astrocytes: transmitter release and membrane signal regulation. Neurochem Res 37:2351–2363
29. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747
30. Zhang Q, Pangrsic T, Kreft M, Krzan M, Li N, Sul JY, Halassa M, Van Bockstaele E, Zorec R, Haydon PG (2004) Fusion-related release of glutamate from astrocytes. J Biol Chem 279:12724–12733
31. Martineau M, Galli T, Baux G, Mothet JP (2008) Confocal imaging and tracking of the exocytotic routes for d-serine-mediated gliotransmission. Glia 56:1271–1284
32. Mothet JP, Pollegioni L, Ouanounou G, Martineau M, Fossier P, Baux G (2005) Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter d-serine. Proc Natl Acad Sci USA 102:5606–5611
33. Krzan M, Stenovec M, Kreft M, Pangrsic T, Grilc S, Haydon PG, Zorec R (2003) Calcium-dependent exocytosis of atrial natriuretic peptide from astrocytes. J Neurosci 23:1580–1583
34. Calegari F, Coco S, Taverna E, Bassetti M, Verderio C, Corradi N, Matteoli M, Rosa P (1999) A regulated secretory pathway in cultured hippocampal astrocytes. J Biol Chem 274:22539–22547
35. Bal-Price A, Moneer Z, Brown GC (2002) Nitric oxide induces rapid, calcium-dependent release of vesicular glutamate and ATP from cultured rat astrocytes. Glia 40:312–323
36. Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C (2003) Storage and release of ATP from astrocytes in culture. J Biol Chem 278:1354–1362
37. Pangrsic T, Potokar M, Stenovec M, Kreft M, Fabbretti E, Nistri A, Pryazhnikov E, Khiroug L, Giniatullin R, Zorec R (2007) Exocytotic release of ATP from cultured astrocytes. J Biol Chem 282:28749–28758
38. Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, Wang W, Gu XS, Duan S (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9:945–953
39. Vardjan N, Gabrijel M, Potokar M, Svajger U, Kreft M, Jeras M, de Pablo Y, Faiz M, Pekny M, Zorec R (2012) IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments. J Neuroinflammation 9:144
40. Parpura V, Verkhratsky A (2012) The astrocyte excitability brief: from receptors to gliotransmission. Neurochem Int 61:610–621
41. 2+ stores in astrocytes. J Neurosci Res 76:86–97
42. 2+ signaling system in astrocytes. PLoS One 5:e11973
43. 2+ waves: mechanisms and function. Physiol Rev 92:1359–1392
44. 2+-dependent glutamate release from rat cortical astrocytes. J Neurosci 28:9682–9691
45. 2+ regulation in neuronal and glial cell signalling. Brain Res Brain Res Rev 26:72–81
46. 2+ channel subtypes in cultured astrocytes. Glia 41:347–353
47. MacVicar BA (1984) Voltage-dependent calcium channels in glial cells. Science 226:1345–1347
48. Parri HR, Crunelli V (2001) Pacemaker calcium oscillations in thalamic astrocytes in situ. Neuroreport 12:3897–3900
49. Lalo U, Pankratov Y, Parpura V, Verkhratsky A (2011) Ionotropic receptors in neuronal-astroglial signalling: what is the role of “excitable” molecules in non-excitable cells. Biochim Biophys Acta 1813:992–1002
50. Rathbone MP, Middlemiss PJ, DeLuca B, Jovetich M (1991) Extracellular guanosine increases astrocyte cAMP: inhibition by adenosine A2 antagonists. Neuroreport 2:661–664
51. Vardjan N, Kreft M, Zorec R (2014) Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes. Glia 62:566–579
52. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477
53. Froese A, Breher SS, Waldeyer C, Schindler RF, Nikolaev VO, Rinné S, Wischmeyer E, Schlueter J, Becher J, Simrick S et al (2012) Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice. J Clin Invest 122:1119–1130
54. Beavo JA, Brunton LL (2002) Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718
55. 2+ signalling: an unexpected complexity. Nat Rev Neurosci 15:327–335
56. Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473
57. Pasti L, Volterra A, Pozzan T, Carmignoto G (1997) Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci 17:7817–7830
58. Hirase H, Qian L, Barthó P, Buzsáki G (2004) Calcium dynamics of cortical astrocytic networks in vivo. PLoS Biol 2:E96
59. Scemes E, Suadicani SO, Spray DC (2000) Intercellular communication in spinal cord astrocytes: fine tuning between gap junctions and P2 nucleotide receptors in calcium wave propagation. J Neurosci 20:1435–1445
60. Bowser DN, Khakh BS (2007) Vesicular ATP is the predominant cause of intercellular calcium waves in astrocytes. J Gen Physiol 129:485–491
61. Jiménez AI, Castro E, Mirabet M, Franco R, Delicado EG, Miras-Portugal MT (1999) Potentiation of ATP calcium responses by A2B receptor stimulation and other signals coupled to Gs proteins in type-1 cerebellar astrocytes. Glia 26:119–128
62. Balázs R, Miller S, Chun Y, O’Toole J, Cotman CW (1998) Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture. J Neurochem 70:2446–2458
63. Bezzi P, Carmignoto G, Pasti L, Vesce S, Rossi D, Rizzini BL, Pozzan T, Volterra A (1998) Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391:281–285
64. Pasti L, Zonta M, Pozzan T, Vicini S, Carmignoto G (2001) Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate. J Neurosci 21:477–484
65. 2+-dependent peptide secretion in astrocytes. J Neurochem 110:143–156
66. Calejo AI, Jorgacevski J, Kucka M, Kreft M, Gonçalves PP, Stojilkovic SS, Zorec R (2013) cAMP-mediated stabilization of fusion pores in cultured rat pituitary lactotrophs. J Neurosci 33:8068–8078
67. Kasai H, Takahashi N, Tokumaru H (2012) Distinct initial SNARE configurations underlying the diversity of exocytosis. Physiol Rev 92:1915–1964
68. Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007) Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331–339
69. Montana V, Malarkey EB, Verderio C, Matteoli M, Parpura V (2006) Vesicular transmitter release from astrocytes. Glia 54:700–715
70. Parpura V, Fang Y, Basarsky T, Jahn R, Haydon PG (1995) Expression of synaptobrevin II, cellubrevin and syntaxin but not SNAP-25 in cultured astrocytes. FEBS Lett 377:489–492
71. Crippa D, Schenk U, Francolini M, Rosa P, Verderio C, Zonta M, Pozzan T, Matteoli M, Carmignoto G (2006) Synaptobrevin2-expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis. J Physiol 570:567–582
72. Maienschein V, Marxen M, Volknandt W, Zimmermann H (1999) A plethora of presynaptic proteins associated with ATP-storing organelles in cultured astrocytes. Glia 26:233–244
73. Wilhelm A, Volknandt W, Langer D, Nolte C, Kettenmann H, Zimmermann H (2004) Localization of SNARE proteins and secretory organelle proteins in astrocytes in vitro and in situ. Neurosci Res 48:249–257
74. Verderio C, Cagnoli C, Bergami M, Francolini M, Schenk U, Colombo A, Riganti L, Frassoni C, Zuccaro E, Danglot L et al (2012) TI-VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes. Biol Cell 104:213–228
75. Hepp R, Perraut M, Chasserot-Golaz S, Galli T, Aunis D, Langley K, Grant NJ (1999) Cultured glial cells express the SNAP-25 analogue SNAP-23. Glia 27:181–187
76. Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon PG (2004) Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci USA 101:9441–9446
77. Südhof TC (2012) Calcium control of neurotransmitter release. Cold Spring Harb Perspect Biol 4:a011353
78. Chen X, Wang L, Zhou Y, Zheng LH, Zhou Z (2005) “Kiss-and-run” glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes. J Neurosci 25:9236–9243
79. Bergersen LH, Gundersen V (2009) Morphological evidence for vesicular glutamate release from astrocytes. Neuroscience 158:260–265
80. Schubert V, Bouvier D, Volterra A (2011) SNARE protein expression in synaptic terminals and astrocytes in the adult hippocampus: a comparative analysis. Glia 59:1472–1488
81. Henneberger C, Papouin T, Oliet SH, Rusakov DA (2010) Long-term potentiation depends on release of d-serine from astrocytes. Nature 463:232–236
82. Perea G, Araque A (2007) Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317:1083–1086
83. Halassa MM, Florian C, Fellin T, Munoz JR, Lee SY, Abel T, Haydon PG, Frank MG (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61:213–219
84. Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116
85. Hines DJ, Haydon PG (2013) Inhibition of a SNARE-sensitive pathway in astrocytes attenuates damage following stroke. J Neurosci 33:4234–4240
86. Lalo U, Palygin O, Rasooli-Nejad S, Andrew J, Haydon PG, Pankratov Y (2014) Exocytosis of ATP from astrocytes modulates phasic and tonic inhibition in the neocortex. PLoS Biol 12:e1001747
87. Nadjar A, Blutstein T, Aubert A, Laye S, Haydon PG (2013) Astrocyte-derived adenosine modulates increased sleep pressure during inflammatory response. Glia 61:724–731
88. Turner JR, Ecke LE, Briand LA, Haydon PG, Blendy JA (2013) Cocaine-related behaviors in mice with deficient gliotransmission. Psychopharmacology 226:167–176
89. Mittelsteadt T, Seifert G, Alvárez-Barón E, Steinhäuser C, Becker AJ, Schoch S (2009) Differential mRNA expression patterns of the synaptotagmin gene family in the rodent brain. J Comp Neurol 512:514–528
90. Singh P, Jorgačevski J, Kreft M, Grubišić V, Stout RF, Potokar M, Parpura V, Zorec R (2014) Single-vesicle architecture of synaptobrevin2 in astrocytes. Nat Commun 5:3780
91. Takamori S, Holt M, Stenius K, Lemke E, Grønborg M, Riedel D, Urlaub H, Schenck S, Brügger B, Ringler P et al (2006) Molecular anatomy of a trafficking organelle. Cell 127:831–846
92. Montana V, Liu W, Mohideen U, Parpura V (2009) Single molecule measurements of mechanical interactions within ternary SNARE complexes and dynamics of their disassembly: SNAP25 versus SNAP23. J Physiol 587:1943–1960
93. Fasshauer D, Antonin W, Margittai M, Pabst S, Jahn R (1999) Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties. J Biol Chem 274:15440–15446
94. Fasshauer D, Sutton RB, Brunger AT, Jahn R (1998) Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs. Proc Natl Acad Sci USA 95:15781–15786
95. Klyachko V, Jackson M (2002) Capacitance steps and fusion pores of small and large-dense-core vesicles in nerve terminals. Nature 418:89–92
96. Parpura V, Zorec R (2010) Gliotransmission: exocytotic release from astrocytes. Brain Res Rev 63:83–92
97. Hertz L, Dringen R, Schousboe A, Robinson SR (1999) Astrocytes: glutamate producers for neurons. J Neurosci Res 57:417–428
98. Martineau M, Shi T, Puyal J, Knolhoff AM, Dulong J, Gasnier B, Klingauf J, Sweedler JV, Jahn R, Mothet JP (2013) Storage and uptake of d-serine into astrocytic synaptic-like vesicles specify gliotransmission. J Neurosci 33:3413–3423
99. Bergersen LH, Morland C, Ormel L, Rinholm JE, Larsson M, Wold JF, Røe AT, Stranna A, Santello M, Bouvier D et al (2012) Immunogold detection of L-glutamate and d-serine in small synaptic-like microvesicles in adult hippocampal astrocytes. Cereb Cortex 22:1690–1697
100. Kang N, Peng H, Yu Y, Stanton PK, Guilarte TR, Kang J (2013) Astrocytes release d-serine by a large vesicle. Neuroscience 240:243–257
101. Sild M, Van Horn MR (2013) Astrocytes use a novel transporter to fill gliotransmitter vesicles with D-serine: evidence for vesicular synergy. J Neurosci 33:10193–10194
102. Burgoyne RD, Morgan A (2003) Secretory granule exocytosis. Physiol Rev 83:581–632
103. Prada I, Marchaland J, Podini P, Magrassi L, D’Alessandro R, Bezzi P, Meldolesi J (2011) REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes. J Cell Biol 193:537–549
104. Paco S, Pozas E, Aguado F (2010) Secretogranin III is an astrocyte granin that is overexpressed in reactive glia. Cereb Cortex 20:1386–1397
105. Ramamoorthy P, Whim MD (2008) Trafficking and fusion of neuropeptide Y-containing dense-core granules in astrocytes. J Neurosci 28:13815–13827
106. Jaiswal JK, Fix M, Takano T, Nedergaard M, Simon SM (2007) Resolving vesicle fusion from lysis to monitor calcium-triggered lysosomal exocytosis in astrocytes. Proc Natl Acad Sci USA 104:14151–14156
107. Liu T, Sun L, Xiong Y, Shang S, Guo N, Teng S, Wang Y, Liu B, Wang C, Wang L et al (2011) Calcium triggers exocytosis from two types of organelles in a single astrocyte. J Neurosci 31:10593–10601
108. Sawada K, Echigo N, Juge N, Miyaji T, Otsuka M, Omote H, Yamamoto A, Moriyama Y (2008) Identification of a vesicular nucleotide transporter. Proc Natl Acad Sci USA 105:5683–5686
109. Oya M, Kitaguchi T, Yanagihara Y, Numano R, Kakeyama M, Ikematsu K, Tsuboi T (2013) Vesicular nucleotide transporter is involved in ATP storage of secretory lysosomes in astrocytes. Biochem Biophys Res Commun 438:145–151
110. Jaiswal JK, Andrews NW, Simon SM (2002) Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells. J Cell Biol 159:625–635
111. Rituper B, Guček A, Jorgačevski J, Flašker A, Kreft M, Zorec R (2013) High-resolution membrane capacitance measurements for the study of exocytosis and endocytosis. Nat Protoc 8:1169–1183
112. Domercq M, Brambilla L, Pilati E, Marchaland J, Volterra A, Bezzi P (2006) P2Y1 receptor-evoked glutamate exocytosis from astrocytes: control by tumor necrosis factor-alpha and prostaglandins. J Biol Chem 281:30684–30696
113. 2+](i) triggers delayed exocytosis of ATP in cultured astrocytes. Glia 56:38–49
114. 2+ transients control exo-endocytosis of synaptic-like microvesicles in astrocytes. J Neurosci 28:9122–9132
115. Miesenböck G, De Angelis D, Rothman J (1998) Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394:192–195
116. Calì C, Marchaland J, Regazzi R, Bezzi P (2008) SDF 1-alpha (CXCL12) triggers glutamate exocytosis from astrocytes on a millisecond time scale: imaging analysis at the single-vesicle level with TIRF microscopy. J Neuroimmunol 198:82–91
117. Santello M, Bezzi P, Volterra A (2011) TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 69:988–1001
118. Bowser DN, Khakh BS (2007) Two forms of single-vesicle astrocyte exocytosis imaged with total internal reflection fluorescence microscopy. Proc Natl Acad Sci USA 104:4212–4217
119. Sankaranarayanan S, Ryan T (2000) Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nat Cell Biol 2:197–204
120. Malarkey EB, Parpura V (2011) Temporal characteristics of vesicular fusion in astrocytes: examination of synaptobrevin 2-laden vesicles at single vesicle resolution. J Physiol 589:4271–4300
121. Sabatini BL, Regehr WG (1999) Timing of synaptic transmission. Annu Rev Physiol 61:521–542
122. Kreft M, Krizaj D, Grilc S, Zorec R (2003) Properties of exocytotic response in vertebrate photoreceptors. J Neurophysiol 90:218–225
123. Potokar M, Vardjan N, Stenovec M, Gabrijel M, Trkov S, Jorgačevski J, Kreft M, Zorec R (2013) Astrocytic vesicle mobility in health and disease. Int J Mol Sci 14:11238–11258
124. 2+ receptor controls the final steps in peptide secretion from pituitary melanotrophs. Neuron 11:93–104
125. Rupnik M, Kreft M, Sikdar SK, Grilc S, Romih R, Zupancic G, Martin TF, Zorec R (2000) Rapid regulated dense-core vesicle exocytosis requires the CAPS protein. Proc Natl Acad Sci USA 97:5627–5632
126. 2+ channels in insulin-secreting mouse pancreatic B cells. Biophys J 81:3308–3323
127. 2+. J Gen Physiol 124:653–662
128. 2+-sensitive pool of vesicles contributes to linearity at the rod photoreceptor ribbon synapse. Neuron 42:595–605
129. Heidelberger R, Heinemann C, Neher E, Matthews G (1994) Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371:513–515
130. Bollmann JH, Sakmann B, Borst JG (2000) Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289:953–957
131. Schneggenburger R, Neher E (2000) Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406:889–893