Ion changes and signalling in perisynaptic glia

ArticleinBrain Research Reviews 63(1-2):113-29 · November 2009with9 Reads
Impact Factor: 5.93 · DOI: 10.1016/j.brainresrev.2009.10.006 · Source: PubMed
Abstract

The maintenance of ion gradients across plasma membranes is a prerequisite for the establishment of cellular membrane potentials, electrical signalling, and metabolite transport. At active synapses, pre- and postsynaptic ion gradients are constantly challenged and used for signalling purposes. Perisynaptic glia, mainly represented by fine processes of astrocytes which get into close vicinity to neuronal synapses, are required to normalize the extracellular ionic milieu and maintain ion gradients. On the other hand, perisynaptic glia itself is activated by synaptically released transmitters binding to plasma membrane receptors and transmitter carriers, and experiences significant ion changes as well. In this review we present an overview of dynamic changes of the major ion species in astrocytes in response to neuronal, especially synaptic, activity. We will focus on calcium, sodium, and proton/hydroxyl ions that play key roles in signalling processes, and will discuss the functional consequences of the glial ion signals and homeostatic processes for synaptic transmission.

    • "In brain, the astrocytes are considered to play a pivotal role in copper homeostasis [2] [8] [9]. Astrocytes represent one of the main brain cell types which fulfills as partner of neurons many important functions, including control of the extracellular environment [10], supply of metabolic substrates to neurons [11] [12], modulation of synaptic transmission and plasticity [13], and protection of the brain against damage caused by oxidants and toxins [14] [15]. "
    [Show abstract] [Hide abstract] ABSTRACT: Copper is essential for several important cellular processes, but an excess of copper can also lead to oxidative damage. In brain, astrocytes are considered to play a pivotal role in the copper homeostasis and antioxidative defence. To investigate whether antioxidants and copper chelators can modulate the uptake and the toxicity of copper ions in brain astrocytes, we used primary astrocytes as cell culture model. These cells accumulated substantial amounts of copper during exposure to copper chloride. Copper accumulation was accompanied by a time- and concentration-dependent loss in cell viability, as demonstrated by a lowering in cellular MTT reduction capacity and by an increase in membrane permeability for propidium iodide. During incubations in the presence of the antioxidants ascorbate, trolox or ebselen, the specific cellular copper content and the toxicity in copper chloride-treated astrocyte cultures were strongly increased. In contrast, the presence of the copper chelators bathocuproine disulfonate or tetrathiomolybdate lowered the cellular copper accumulation and the copper-induced as well as the ascorbate-accelerated copper toxicity was fully prevented. These data suggest that predominantly the cellular content of copper determines copper-induced toxicity in brain astrocytes. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · Oct 2015 · Journal of Trace Elements in Medicine and Biology
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    • "In brain, the astrocytes are considered to play a pivotal role in copper homeostasis [2] [8] [9]. Astrocytes represent one of the main brain cell types which fulfills as partner of neurons many important functions, including control of the extracellular environment [10], supply of metabolic substrates to neurons [11] [12], modulation of synaptic transmission and plasticity [13], and protection of the brain against damage caused by oxidants and toxins [14] [15]. "
    [Show abstract] [Hide abstract] ABSTRACT: Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism.
    No preview · Article · Aug 2015 · Neurochemical Research
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    • ", which are fundamental for intracellular pH and ion homeostasis [41]. Therefore, dynamic [Na + ] i regulates diverse homeostatic roles of astrocytes, including neurotransmitter uptake, K + buffering, and cell metabolism [34,42,43] . "
    [Show abstract] [Hide abstract] ABSTRACT: Intracellular Ca(2+) elevation resulting from different Ca(2+) pathways may play different roles in astrocyte functions. Channelrhodopsin-2 (ChR2), a light-gated cation channel, has been used to selectively stimulate astrocytes by inducing intracellular Ca(2+) ([Ca(2+)]i) elevation, but the exact underlying mechanism is still unclear. We found that in the absence of extracellular Ca(2+), light stimulation failed to induce [Ca(2+)]i elevation in astrocytes expressed ChR2. Pharmacological experiments excluded the involvement of Ca(2+)-induced Ca(2+) release from intracellular stores. Further experiments demonstrated that the ChR2-induced [Ca(2+)]i elevation was mainly mediated by reversal of the Na(+)-Ca(2+) exchanger following Na(+) influx through ChR2 channels. Since intracellular Na(+) homeostasis plays important roles in astrocytes, including the modulation of [Ca(2+)]i, neurotransmitter uptake and cell metabolism, our results indicate that ChR2 is a good candidate which could be used for mimicking the intracellular Na(+) disturbance in astrocytes that occurs in various physiological and pathological processes including the uptake of neurotransmitters and ischemia, as well as the activities of various cation channels, ion exchangers, and pumps. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Cell calcium
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