Deletion of Cav2.1(α1A) subunit of Ca2+-channels impairs synaptic GABA and glutamate release in the mouse cerebellar cortex in cultured slices

2009 ◽  
Vol 30 (12) ◽  
pp. 2293-2307 ◽  
Author(s):  
Etienne Lonchamp ◽  
Jean-Luc Dupont ◽  
Frédéric Doussau ◽  
Hee-Sup Shin ◽  
Bernard Poulain ◽  
...  
Keyword(s):  
Cerebellar Cortex ◽  
Glutamate Release ◽  
Cultured Slices ◽  
Ca2 Channels

Glutamate microinjections in cerebellar cortex reproduce cerebrovascular effects of parallel fiber stimulation

1996 ◽  
Vol 271 (6) ◽  
pp. R1568-R1575 ◽  
Author(s):  
G. Yang ◽  
C. Iadecola
Keyword(s):  
Glutamate Receptors ◽  
Cerebellar Cortex ◽  
Glutamate Release ◽  
Molecular Layer ◽  
Parallel Fiber ◽  
Synaptic Activity ◽  
No Production ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Fiber Stimulation

Electrical stimulation of cerebellar parallel fibers releases glutamate and increases local blood flow (BFcrb), an effect in part mediated by glutamate-induced nitric oxide (NO) production. We studied whether local microinjection of glutamate into the cerebellar cortex would produce increases in BFcrb comparable to those elicited by parallel fiber stimulation. In halothane-anesthetized rats equipped with a cranial window, glutamate was microinjected into the cerebellar molecular layer, and BFcrb was monitored by laser-Doppler flowmetry. Glutamate microinjections increased BFcrb dose dependently (2-200 pmol in 200 nl) (n = 9) and by 55 +/- 6% at 200 pmol (mean +/- SE). The magnitude and temporal profile of the increases in BFcrb compared favorably with the increase in flow produced by parallel fiber stimulation. The glutamate-induced BFcrb increase was attenuated by superfusion with the Na2+ channel blocker tetrodotoxin (10 microM; -50 +/- 10%; n = 5; P < 0.05; t-test) or by blocking synaptic activity by treatment of the cerebellar cortex with Ringer containing 20 mM Mg2+ and 0 mM Ca2+ (-80 +/- 4%; n = 6; P < 0.05). The glutamate-receptor antagonist kynurenate (10 mM) attenuated the increase in BFcrb by 59 +/- 6% (P < 0.05; n = 5). The relatively selective inhibitor of neuronal NO synthase 7-nitroindazole (100 mg/kg ip) reduced the flow response evoked by microinjection of glutamate (-46 +/- 7%; n = 5; P < 0.05) but not acetylcholine (10 microM; P > 0.05; n = 6). We conclude that glutamate microinjections increase local BFcrb via activation of glutamate receptors. The glutamate-induced vasodilation is mediated, in part, by neurally derived NO. The striking similarities between the vascular responses evoked by parallel fiber stimulation and that produced by microinjection of glutamate support the hypothesis that the increase in BFcrb produced by parallel fiber stimulation is mediated by glutamate release and activation of glutamate receptors. The data also strengthen the hypothesis that glutamate and NO are important mediators in the mechanisms linking synaptic activity to BFcrb in cerebellar cortex.

Potentiation of mGlu7 receptor-mediated glutamate release at nerve terminals containing N and P/Q type Ca2+ channels

2013 ◽  
Vol 67 ◽  
pp. 213-222 ◽  
Author(s):  
José Javier Ferrero ◽  
David Bartolomé-Martín ◽  
Magdalena Torres ◽  
José Sánchez-Prieto
Keyword(s):  
Glutamate Release ◽  
Nerve Terminals ◽  
Ca2 Channels

Asynchronous Glutamate Release at Autapses Regulates Spike Reliability and Precision in Mouse Neocortical Pyramidal Cells

2020 ◽  
Author(s):  
Junlong Li ◽  
Suixin Deng ◽  
Quansheng He ◽  
Wei Ke ◽  
Yousheng Shu
Keyword(s):  
Prefrontal Cortex ◽  
Glutamate Release ◽  
Pyramidal Cells ◽  
Essential Elements ◽  
Temporal Precision ◽  
Spike Reliability ◽  
Asynchronous Release ◽  
Whole Cell Recordings ◽  
Ca2 Channels ◽  
Cortical Information Processing

Abstract Autapses are self-synapses of a neuron. Inhibitory autapses in the neocortex release GABA in 2 modes, synchronous release and asynchronous release (AR), providing precise and prolonged self-inhibition, respectively. A subpopulation of neocortical pyramidal cells (PCs) also forms functional autapses, activation of which promotes burst firing by strong unitary autaptic response that reflects synchronous glutamate release. However, it remains unclear whether AR occurs at PC autapses and plays a role in neuronal signaling. We performed whole-cell recordings from layer-5 PCs in slices of mouse prefrontal cortex (PFC). In response to action potential (AP) burst, 63% of PCs showed robust long-lasting autaptic AR, much stronger than synaptic AR between neighboring PCs. The autaptic AR is mediated predominantly by P/Q-type Ca2+ channels, and its strength depends on the intensity of PC activity and the level of residual Ca2+. Further experiments revealed that autaptic AR enhances spiking activities but reduces the temporal precision of post-burst APs. Together, the results show the occurrence of AR at PC autapses, the delayed and persistent glutamate AR causes self-excitation in individual PCs but may desynchronize the autaptic PC population. Thus, glutamatergic autapses should be essential elements in PFC and contribute to cortical information processing.

Neuroprotective Role of the B Vitamins in the Modulation of the Central Glutamatergic Neurotransmission

2021 ◽  
Vol 20 ◽  
Author(s):  
Shu-Kuei Huang ◽  
Cheng-Wei Lu ◽  
Tzu-Yu Lin ◽  
Su-Jane Wang
Keyword(s):  
Glutamate Release ◽  
B Vitamins ◽  
Nerve Terminals ◽  
Normal Brain ◽  
Membrane Excitability ◽  
Presynaptic Nerve Terminal ◽  
Normal Brain Function ◽  
Vesicular Exocytosis ◽  
Presynaptic Nerve Terminals ◽  
Ca2 Channels

Background: Regulation of glutamate release is crucial for maintaining normal brain function, but excess glutamate release is implicated in many neuropathological conditions. Therefore, the minimum glutamate release from presynaptic nerve terminals is an important neuroprotective mechanism. Objective: In this mini-review, we analyze the three B vitamins, namely vitamin B2 (riboflavin), vitamin B6 (pyridoxine), and vitamin B12 (cyanocobalamin), that affect the 4-aminopyridine (4-AP)-evoked glutamate release from presynaptic nerve terminal in rat and discuss their neuroprotective role. Methods: In this study, the measurements include glutamate release, DiSC3(5), and Fura-2. Results: The riboflavin, pyridoxine, and cyanocobalamin produced significant inhibitory effects on 4-aminopyridine-evoked glutamate release from rat cerebrocortical nerve terminals (synaptosomes) in a dose-dependent relationship. These presynaptic inhibitory actions of glutamate release are attributed to inhibition of physiologic Ca2+-dependent vesicular exocytosis but not Ca2+-independent nonvesicular release. These effects also did not affect membrane excitability, while diminished cytosolic [Ca2+]c through a reduction of direct Ca2+ influx via Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, rather than through indirect Ca2+ induced Ca2+ release from ryanodine-sensitive intracellular stores. Furthermore, their effects were attenuated by GF109203X and Ro318220, two protein kinase C (PKC) inhibitors, suggesting suppression of PKC activity. Taken together, these results suggest that riboflavin, pyridoxine, and cyanocobalamin inhibit presynaptic vesicular glutamate release from rat cerebrocortical synaptosomes, through the depression Ca2+ influx via voltage-dependent Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, and PKC signaling cascade. Conclusion: Therefore, these B vitamins may reduce the strength of glutamatergic synaptic transmission and is of considerable importance as potential targets for therapeutic agents in glutamate-induced excitation-related diseases.

Widespread Inhibition of Sodium Channel–dependent Glutamate Release from Isolated Nerve Terminals by Isoflurane and Propofol

2001 ◽  
Vol 95 (6) ◽  
pp. 1460-1466 ◽  
Author(s):  
Ratnakumari Lingamaneni ◽  
Martin L. Birch ◽  
Hugh C. Hemmings
Keyword(s):  
Cerebral Cortex ◽  
Guinea Pig ◽  
Rat Brain ◽  
Glutamate Release ◽  
Brain Regions ◽  
Rat Striatum ◽  
Nerve Terminals ◽  
Na Channels ◽  
Rat Brain Regions ◽  
Ca2 Channels

Background Controversy persists concerning the mechanisms and role of general anesthetic inhibition of glutamate release from nerve endings. To determine the generality of this effect and to control for methodologic differences between previous studies, the authors analyzed the presynaptic effects of isoflurane and propofol on glutamate release from nerve terminals isolated from several species and brain regions. Methods Synaptosomes were prepared from rat, mouse, or guinea pig cerebral cortex and also from rat striatum and hippocampus. Release of endogenous glutamate evoked by depolarization with 20 microm veratridine (which opens voltage-dependent Na+ channels by preventing inactivation) or by 30 mm KCl (which activates voltage-gated Ca2+ channels by membrane depolarization) was monitored using an on-line enzyme-linked fluorometric assay. Results Glutamate release evoked by depolarization with increased extracellular KCl was not significantly inhibited by isoflurane up to 0.7 mM ( approximately 2 minimum alveolar concentration; drug concentration for half-maximal inhibition [IC50] &gt; 1.5 mM) [corrected] or propofol up to 40 microm in synaptosomes prepared from rat, mouse, or guinea pig cerebral cortex, rat hippocampus, or rat striatum. Lower concentrations of isoflurane or propofol significantly inhibited veratridine-evoked glutamate release in all three species (isoflurane IC50 = 0.41-0.50 mm; propofol IC50 = 11-18 microm) and rat brain regions. Glutamate release was evoked by veratridine or increased KCl (from 5 to 35 mM) to assess the involvement of presynaptic ion channels as targets for drug actions [corrected]. Conclusions Isoflurane and propofol inhibited Na+ channel-mediated glutamate release evoked by veratridine with greater potency than release evoked by increased KCl in synaptosomes prepared from three mammalian species and three rat brain regions. These findings are consistent with a greater sensitivity to anesthetics of presynaptic Na+ channels than of Ca2+ channels coupled to glutamate release. This widespread presynaptic action of general anesthetics is not mediated by potentiation of gamma-aminobutyric acid type A receptors, though additional mechanisms may be involved.

scholarly journals Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels

2013 ◽  
Vol 16 (12) ◽  
pp. 1754-1763 ◽  
Author(s):  
Yaroslav S Ermolyuk ◽  
Felicity G Alder ◽  
Rainer Surges ◽  
Ivan Y Pavlov ◽  
Yulia Timofeeva ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Ca2 Channels

Volatile Anesthetics Depress Calcium sup 2+ Transients and Glutamate Release in Isolated Cerebral Synaptosomes

1995 ◽  
Vol 83 (3) ◽  
pp. 593-603. ◽  
Author(s):  
Ning Miao ◽  
Martha J. Frazer ◽  
Carl III Lynch
Keyword(s):  
Minimum Alveolar Concentration ◽  
Glutamate Release ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Volatile Anesthetics ◽  
Buffer Solution ◽  
Dose Dependent Fashion ◽  
The Central Nervous System ◽  
Dose Dependent ◽  
Ca2 Channels ◽  
External K

Background The current study was performed to determine whether volatile anesthetics may include as part of their action in the central nervous system the depression of presynaptic transmitter release by alteration in intrasynaptic [Ca2+] ([Ca2+]i). Methods Guinea pig cerebrocortical synaptosomes were studied at 37 degrees C suspended in control buffer solution containing 1.3 mM external [Ca2+] ([Ca2+]e). Spectrofluorometric assays were used to monitor [Ca2+]i with the Ca(2+)-sensitive fluorophore Fura-2 and to monitor glutamate release with an enzyme-coupled assay that produced the fluorescent product nicotinamide adenine dinucleotide phosphate. To activate the increase in [Ca2+]i and glutamate release, synaptosomes were depolarized by abruptly increasing external [K+] from 5 to 35 mM. Responses were determined in solutions equilibrated with approximately 1 or 2 minimum alveolar concentration (MAC) isoflurane, enflurane, or halothane and also in solutions with decreased [Ca2+]e (0.025, 0.05, 0.1, 0.2, 0.4, and 0.6 mM). Results Although they had no action on basal behavior, the anesthetics depressed the K(+)-depolarization-induced increase in both [Ca2+]i and glutamate release in a dose-dependent fashion. The [Ca2+]i transient was inhibited by 13-21% per MAC, and glutamate release was depressed 14-28% per MAC. The depression of both [Ca2+]i and glutamate release caused by 2.5% isoflurane, 3.4% enflurane, and 1.5% halothane could be reproduced by a reduction in [Ca2+]e to 0.2-0.4 mM. Conclusions In this setting, isoflurane, enflurane, and halothane decrease [Ca2+]i in a manner consistent with inhibition of Ca2+ entry, possibly by specific voltage-gated neuronal Ca2+ channels. This decrease in [Ca2+]i is sufficient to account for all or most of the associated decrease in glutamate release.

Sign in / Sign up

Export Citation Format

Share Document