The relationship between cytoplasmic free Ca2+ and the release of glutamate from synaptosomes

McMahon, Harvey T.; Nicholls, David G.

doi:10.1042/bst0180375

Cited by 11 publications

(7 citation statements)

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“…We used synaptosomes to isolate the specific contribution of the presynaptic component for ATP release, which can be triggered with a chemically induced depolarization, using increasing extracellular K + in the range of 5–60 mM [ 32 , 33 ]. Accordingly, K + (10–60 mM) triggered a concentration-dependent enhancement of ATP release from mouse striatal synaptosomes (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2A ). Notably, whereas the release of classical neurotransmitters such as glutamate or GABA from synaptosomes reaches a near maximal value at 30 mM K + [ 32 , 33 ], the evoked ATP release was lower when using lower extracellular K + concentrations (6.82 ± 1.22 and 12.08 ± 1.69 pmol/mg protein, n = 6–9, at 10–30 mM K + ) and was larger when triggered with a higher K + extracellular concentration (60 mM: 29.24 ± 2.59 pmol/mg protein, n = 6) (Fig. 2A ).…”

Section: Resultsmentioning

confidence: 99%

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Increased ATP Release and Higher Impact of Adenosine A2A Receptors on Corticostriatal Plasticity in a Rat Model of Presymptomatic Parkinson’s Disease

et al. 2022

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Extracellular ATP can be a danger signal, but its role in striatal circuits afflicted in Parkinson’s disease (PD) is unclear and was now investigated. ATP was particularly released at high stimulation intensities from purified striatal nerve terminals of mice, which were endowed with different ATP-P2 receptors (P2R), although P2R antagonists did not alter corticostriatal transmission or plasticity. Instead, ATP was extracellularly catabolized into adenosine through CD73 to activate adenosine A2A receptors (A2AR) modulating corticostriatal long-term potentiation (LTP) in mice. In the presymptomatic phase of a 6-hydroxydopamine rat model of PD, ATP release from striatal nerve terminals was increased and was responsible for a greater impact of CD73 and A2AR on corticostriatal LTP. These observations identify increased ATP release and ATP-derived formation of extracellular adenosine bolstering A2AR activation as a key pathway responsible for abnormal synaptic plasticity in circuits involved in the onset of PD motor symptoms. The translation of these findings to humans prompts extending the use of A2AR antagonists from only co-adjuvants of motor control in Parkinsonian patients to neuroprotective drugs delaying the onset of motor symptoms.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Increased ATP Release and Higher Impact of Adenosine A2A Receptors on Corticostriatal Plasticity in a Rat Model of Presymptomatic Parkinson’s Disease

et al. 2022

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“…Through a process of homogenization and centrifugation (49), the nerve terminals are pinched off and resealed (Fig.2). The synaptosomes contain mitochondria and are able to maintain the ATP levels for more than 6 hours when kept on ice (49,50). Preserved in a medium with a low K + concentration, they maintain a membrane potensial of -60 mV to -80mV (51) and a cytoplasmic free Ca 2+ concentration of 0.1-0.2 PM (52).…”

Section: The Synaptosomal Preparationmentioning

confidence: 99%

Sevoflurane depolarizes pre‐synaptic mitochondria in the central nervous system

Moe¹,

Bains²,

Vinje³

et al. 2004

Acta Anaesthesiol Scand

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Background: Volatile anaesthetics protect the heart from ischaemic injury by activating mitochondrial signalling pathways. The aim of this study was to test whether sevoflurane, which is increasingly used in neuroanaesthesia, affects mitochondrial function in the central nervous system by altering the mitochondrial membrane potential (ΔΨm).Methods: In order to correlate free cytosolic Ca2+ ([Ca2+]i) and ΔΨm, rat neural presynaptic terminals (synaptosomes) were loaded with the fluorescent probes fura‐2 and JC‐1. During sevoflurane exposure, 4‐aminopyridine (4‐AP) 500 µM to induce pre‐synaptic membrane depolarization or carbonylcyanide‐p‐(trifluoromethoxy)‐phenylhydrazone (FCCP) 1 µM to induce maximum mitochondrial depolarization was added. In order to block mitochondrial ATP‐regulated K+‐channels (mitoKATP), the antagonist 5‐hydroxydecanoate (5‐HD) 500 µM was added.Results: In Ca2+‐containing medium, both sevoflurane 1 and 2 MAC gradually decreased the normalized JC‐1 ratio from 0.96 ± 0.01 in control to 0.92 ± 0.01 and 0.89 ± 0.01, representing a depolarization of ΔΨm (n = 9, P < 0.05). Sevoflurane 2 MAC increased [Ca2+]i. In Ca2+‐depleted medium, sevoflurane 1 and 2 MAC depolarized ΔΨm, while [Ca2+]i remained unaltered. Sevoflurane 2 MAC attenuated the 4‐AP‐induced depolarization of ΔΨm. When mitoKATP was blocked, the sevoflurane‐induced depolarization of ΔΨm was attenuated, but not blocked. The depolarizing effect of sevoflurane on ΔΨm compared with FCCP was calculated to 13.2 ± 1.3% in Ca2+‐containing and 15.1 ± 1.2% in Ca2+‐depleted medium (n = 7).Conclusions: Sevoflurane depolarizes ΔΨm in rat synaptosomes, and the effect is not dependent on Ca2+‐influx to the cytosol. Opening of mitoKATP is partly responsible for the depolarizing effect of sevoflurane.

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“…It is well established that glutamate is physiologically released by both exocytosis and reversal of high-affinity uptake transporters (McMahon and Nicholls 1989). Both release mechanisms require, among others, depolarization of the plasma membrane which can be induced by different stimulation conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Glutamate is the most abundant neurotransmitter in the mammalian brain and mediates fast excitatory neurotransmission (McMahon and Nicholls 1989). Besides its involvement in cognitive processes (Larkman and Jack 1995), glutamate also plays a major role-together with the inhibitory neurotransmitter GABA-in the pathophysiology of epilepsy (Meldrum 1994).…”

Section: Introductionmentioning

confidence: 99%

Effects of antiepileptic drugs on glutamate release from rat and human neocortical synaptosomes

Kammerer

Brawek

Freiman

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Aim of this study was to learn whether the antiepileptic drugs (AEDs) carbamazepine, lamotrigine, phenytoin, gabapentin, pregabalin, levetiracetam, and valproate (all at 100 μM) presynaptically influence the neurotransmission of the excitatory transmitter glutamate. The effects of these frequently used AEDs were examined on ³H-glutamate release from superfused synaptosomes of both rat and human neocortex. Release was evoked by elevation of buffer [K(+)] from 3 to 15 mM or by the Na(+) channel activator veratridine (1, 3.2, and 10 μM). Buffer [K(+)] elevation induced ³H-glutamate exocytosis, which was Ca(²+)-, but not Na(+)-, dependent and which was accompanied only in human tissue by release through transporter reversal. In rat tissue, release was diminished by the Na(+) channel inhibitors carbamazepine, lamotrigine, and phenytoin, which therefore may also affect presynaptic Ca(²+) channels. Interestingly, levetiracetam increased ³H-glutamate release. In contrast, the tested AEDs did not affect K(+)-evoked ³H-glutamate release in human tissue, neither when the transporters were operative nor when exocytosis was isolated by transporter blockade. Veratridine-evoked ³H-glutamate release was a Na(+)-dependent transmitter efflux through reversed transporters in both species which in human synaptosomes was accompanied by exocytosis. The latter depended on external Ca(²+). Carbamazepine, lamotrigine, and phenytoin reduced this release from both rat and human tissue. There is an obvious species difference in the effects of carbamazepine, lamotrigine, and phenytoin on K(+)-evoked ³H-glutamate release while their inhibitory effects on veratridine-evoked release were similar. Thus, the depression of ³H-glutamate release by carbamazepine, lamotrigine, and phenytoin may be due to inhibited synaptosomal Na(+) or Ca(²+) influx.

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The relationship between cytoplasmic free Ca2+ and the release of glutamate from synaptosomes

Cited by 11 publications

References 1 publication

Increased ATP Release and Higher Impact of Adenosine A2A Receptors on Corticostriatal Plasticity in a Rat Model of Presymptomatic Parkinson’s Disease

Increased ATP Release and Higher Impact of Adenosine A2A Receptors on Corticostriatal Plasticity in a Rat Model of Presymptomatic Parkinson’s Disease

Sevoflurane depolarizes pre‐synaptic mitochondria in the central nervous system

Effects of antiepileptic drugs on glutamate release from rat and human neocortical synaptosomes

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