Roles of Na
 +
 –Ca
 2+
 exchange and of mitochondria in the regulation of presynaptic Ca
 2+
 and spontaneous glutamate release

Scotti, Alessandra L.; Chatton, Jean–Yves; Réuter, H.

doi:10.1098/rstb.1999.0387

Cited by 43 publications

(31 citation statements)

References 36 publications

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“…Comparable data from mammalian CNS synapses are scarce. However, after inhibition of Na + -Ca 2+ exchange, calcium dynamics differ substantially at different synapses and this heterogeneity disappears after inhibition of mitochondrial function, suggesting that mitochondria buffer presynaptic calcium at a subpopulation of hippocampal synapses [4,16,19]. Whether mitochondria buffer presynaptic calcium in hippocampal terminals when Na + -Ca 2+ exchange is intact is unclear.…”

Section: Introductionmentioning

confidence: 92%

Mitochondria and release at hippocampal synapses

Waters

Smith

2003

Pfl�gers Archiv European Journal of Physiology

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Mitochondria are present in some, but not all presynaptic terminals in the hippocampus. Mitochondria are capable of sequestering and storing large amounts of calcium, but it is unclear whether they influence release probability at these synapses. Using FM dye imaging techniques and confocal microscopy, we have examined the relationship between mitochondrial presence/absence and presynaptic vesicle release from rat hippocampal neurones in primary dissociated culture at room temperature. Following staining with the mitochondrial dye mitotracker green, we were able to resolve putative individual mitochondria associated with neuronal processes. The majority of mitochondria were positionally stable, although some exhibited periods of rapid motility (up to 0.4 microm/s) interspersed with periods of immobility. Co-staining with mitotracker green and the synaptic vesicle dye FM 4-64 indicated that 180 of 506 (36%) synapses were devoid of mitochondria. A comparison of vesicular release in response to stimulation at 1 Hz and at 10 Hz revealed no differences in release properties between synapses with and without mitochondria.

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Section: Introductionmentioning

confidence: 92%

Mitochondria and release at hippocampal synapses

Waters

Smith

2003

Pfl�gers Archiv European Journal of Physiology

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“…Hippocampi were dissected from the brain of neonatal Sprague-Dawley rats (P0-2). Dissociation of cells and culturing procedures have been extensively described before (15).…”

Section: Methodsmentioning

confidence: 99%

“…FM4-64 puncta were identified as functional presynaptic boutons when the dye could be released in response to a second period of stimulation (90 s, 20 Hz) (12,15,20). FM4-64 was excited by the HeNe laser (543 nm) and its emission was long pass-filtered above 585 nm.…”

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confidence: 99%

Synaptic and extrasynaptic γ-aminobutyric acid type A receptor clusters in rat hippocampal cultures during development

Scotti

Réuter

2001

Proc. Natl. Acad. Sci. U.S.A.

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We have simultaneously measured the expression of postsynaptic ␥-aminobutyric acid type A (GABAA) receptor clusters and of presynaptic boutons in neonatal rat hippocampal cultures between days 1 and 30. GABA A receptors were labeled with antibodies recognizing the extracellular domains of ␤2͞3 and ␥2 subunits. Boutons were visualized by activity-dependent uptake of the styryl dye FM4-64, or by antibodies against the presynaptic vesicular protein SV2 or the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). GABA A receptor clusters could be seen in living neurons already 6 h after culturing, much before presynaptic markers could be identified in nerve terminals. The densities of receptor clusters that contained the ␤2͞3 subunits were constant between days 10 and 30 in culture, whereas ␥2 subunit-containing clusters fluctuated and reached a maximum on day 20. SV2 and GAD staining could be measured from day 2 onwards. Clustering of GAD in presynaptic terminals and FM4-64 uptake were observed only at day 5 and afterward. SV2 staining and FM4-64 uptake increased in parallel between days 5 and 20 and remained constant thereafter. GAD-stained boutons were fewer than those labeled with other, less specific, presynaptic stains. They reached a maximum on day 20 and fell again toward day 30. Double labeling of GABA A receptors and of presynaptic boutons in neurons during differentiation showed that, even after 30 days in culture, large fractions of GABA A receptor clusters containing ␤2͞3 and͞or ␥2 subunits remained extrasynaptic. T he type A receptors for ␥-aminobutyric acid (GABA A receptors) are ligand-gated ion channels that mediate synaptic inhibition. These chloride channels are heteropentameric structures and can be assembled from a multitude of subunits (␣1-6, ␤1-3, ␥1-3, ␦, , , ). Some subunit combinations are very common and widely distributed in the nervous system, whereas others are restricted to specific neuronal populations (1-4). The GABA A receptor subunit combinations that are most frequently observed in hippocampal granular and pyramidal cells are ␣2␤2͞3␥2 and ␣1␤2͞3␥2. The ␤1 subunit, although less frequent, has a similar distribution as ␤3. The ␣1 and the ␤2 subunits are particularly enriched in interneurons of the hippocampus, where they colocalize with the ␥2 subunit (1, 5, 6). In the rat hippocampus, the ␤2͞3 subunits are present at early stages of embryonal development, whereas expression of ␥2 increases only after birth to moderate levels (7).There is increasing evidence for extrasynaptic GABA A receptors in neurons of the adult brain (8-11), and it was recently found (12) that, in hippocampal cultures, only about 50% of GABA A receptor clusters correlated with apposed presynaptic boutons. Furthermore, recent electrophysiological results from brain slices have shown that ion conductances and kinetics of currents through synaptic and extrasynaptic GABA-activated channels are quite different, which may be important for neuronal function in vivo (8,9).In the present study, GABA A receptor clu...

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“…The most important intraterminal element responsible for presynaptic Ca 2ϩ homeostasis is the mitochondrion (23), initially identified in a series of in-depth biochemical studies (78). Nearly all mature, active presynaptic terminals contain mitochondria, although their localization is highly dynamic (79), leading to their (transient) absence from some presynaptic sites in the brain (80).…”

Section: Discussionmentioning

confidence: 99%

A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange

Nichols

Dengler

Nakagawa³

et al. 2007

Journal of Biological Chemistry

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Roles of Na ⁺ –Ca ²⁺ exchange and of mitochondria in the regulation of presynaptic Ca ²⁺ and spontaneous glutamate release

Cited by 43 publications

References 36 publications

Mitochondria and release at hippocampal synapses

Mitochondria and release at hippocampal synapses

Synaptic and extrasynaptic γ-aminobutyric acid type A receptor clusters in rat hippocampal cultures during development

A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange

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Roles of Na + –Ca 2+ exchange and of mitochondria in the regulation of presynaptic Ca 2+ and spontaneous glutamate release

Cited by 43 publications

References 36 publications

Mitochondria and release at hippocampal synapses

Mitochondria and release at hippocampal synapses

Synaptic and extrasynaptic γ-aminobutyric acid type A receptor clusters in rat hippocampal cultures during development

A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange

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Roles of Na ⁺ –Ca ²⁺ exchange and of mitochondria in the regulation of presynaptic Ca ²⁺ and spontaneous glutamate release