Mechanisms in the regulation of neurotransmitter release from brain nerve terminals: Current hypotheses

Sihra, Talvinder S.; Nichols, Robert A.

doi:10.1007/bf00966922

Cited by 60 publications

(24 citation statements)

References 207 publications

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“…Since depression of evoked release occurs under conditions in which one would expect the levels of Ca2+ in the nerve terminal to be increased, perhaps depression results from the inactivation or saturation of a Ca2+-sensitive factor or site involved in the synchronization of evoked release. Candidates for such a calcium-binding site include one of the recently described cytoplasmic proteins that are thought to be involved in the regulation of evoked release (reviewed in Sihra & Nichols, 1993), and, of course, the calcium channel itself (Eckert & Chad, 1984). Interestingly, there is evidence in Aplysia that the time course of depression is very similar to the time course of inactivation of presynaptic calcium currents (Klein, Shapiro & Kandel, 1980).…”

Section: Discussionmentioning

confidence: 99%

Changes in MEPP frequency during depression of evoked release at the frog neuromuscular junction.

Zengel

Sosa

1994

The Journal of Physiology

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1. Endplate potentials (EPPs) and miniature endplate potentials (MEPPs) were recorded from frog neuromuscular junctions bathed in Ringer solutions containing normal (1P8 mM) or high (3-6 mM) Ca2". The peptide toxin /s-conotoxin GIIIA was added to the Ringer solution to prevent muscle action potentials and contraction. 2. The nerve was stimulated with conditioning trains of 200-4800 impulses applied at 20 impulses s' to characterize the effects of repetitive stimulation on changes in EPP amplitude and MEPP frequency under high quantal conditions. 3. MEPP frequency was dramatically increased during and immediately following repetitive stimulation under high quantal conditions, whereas EPP amplitude was greatly depressed. There was no effect of repetitive stimulation on MEPP amplitude. 4. Following the conditioning stimulation the increase in MEPP frequency decayed back to the control level with a time course that could be described by four exponentials. The time constants of these exponentials were very similar to those that describe the components of stimulation-induced increases in EPP amplitude and MEPP frequency observed under low quantal conditions when depression is absent. 5. The results of this study indicate that depression and the components of stimulationinduced increases in release (facilitation, augmentation and potentiation) can be present at the same time, suggesting that the mechanism of depression involves different underlying factors from the mechanism(s) responsible for increases in release. They also indicate either that depression selectively affects only those quanta destined to be released in direct response to the nerve action potential, which would suggest that EPPs and MEPPs arise from different pools of transmitter, or that depression in some way affects a step in the release process involved only in evoked release, and not asynchronous (spontaneous) release.

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Section: Discussionmentioning

confidence: 99%

Changes in MEPP frequency during depression of evoked release at the frog neuromuscular junction.

Zengel

Sosa

1994

The Journal of Physiology

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“…12,34,35 Therefore, when addressing the mechanism responsible for the ferulic acidmediated inhibition of Ca 2 + -dependent glutamate release, this study considered two scenarios that might be involved: (1) alteration of the synaptosomal plasma membrane potential and downstream modulation of Ca 2 + influx into the terminal, and (2) entry. The first possibility is unlikely for three reasons.…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

Lin

Huang

et al. 2013

Journal of Medicinal Food

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This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K + channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca 2 + ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca 2 + concentration, but did not alter 4-AP-mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na + /Ca 2 + exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca 2 + entry.

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“…Since our data suggest that, in Dictyostelium, VPA reduces the phospholipid-dependent signaling and vesicle release, we examined an effect of VPA and PI3K inhibition in the modulation of synaptic signaling. We thus assessed the effect of VPA and a PI3K inhibitor on depolarization-dependent neurotransmitter glutamate release from isolated rat cerebrocortical nerve terminals (synaptosomes), an established model for assessing presynaptic function (54). In this model, VPA dose dependently inhibited 4-aminopyridineevoked glutamate release from synaptosomes (Fig.…”

Section: Resultsmentioning

confidence: 99%

Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid

Müller‐Taubenberger

Adley

et al. 2007

Eukaryot Cell

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Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH Crac -green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP 3 ) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP 2 phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP 3 production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.

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Mechanisms in the regulation of neurotransmitter release from brain nerve terminals: Current hypotheses

Cited by 60 publications

References 207 publications

Changes in MEPP frequency during depression of evoked release at the frog neuromuscular junction.

Changes in MEPP frequency during depression of evoked release at the frog neuromuscular junction.

Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid

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