Ion changes and signalling in perisynaptic glia

Abteilung für Allgemeine Zoologie, FB Biologie, TU Kaiserslautern, D-67653 Kaiserslautern, Germany.
Brain Research Reviews (Impact Factor: 5.93). 11/2009; 63(1-2):113-29. DOI: 10.1016/j.brainresrev.2009.10.006
Source: PubMed


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.

9 Reads
    • "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.
    Journal of Trace Elements in Medicine and Biology 10/2015; 32:168-76. DOI:10.1016/j.jtemb.2015.07.001 · 2.37 Impact Factor
  • Source
    • "The most primary and fundamental astroglial function lies in providing the homeostasis of the central nervous system (CNS). Numerous molecular cascades expressed (often specifically) in astrocytes control interstitial concentration of principal ions, regulate movement and metabolism of major neurotransmitters, supply neurones with energy substrates and contribute to tissue defence through, for example, secreting scavengers of reactive oxygen species (Deitmer and Rose, 2010; Rose et al., 2013; Verkhratsky et al., 2015). Astroglial cells are involved in regulation of interstitial pH by transporting both protons (mostly through sodium-proton transporter 1, NHE1, glutamate transporters EAAT1/2 and proton-lactate co-transporter MCT1) and bicarbonate (through the sodium-bicarbonate co-transporter NBC or the chloride-bicarbonate exchanger AE; see (Deitmer and Chesler, 2009; Deitmer and Rose, 2010)). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical evidence suggest astrocytic abnormality in major depression (MD) while treatment with anti-psychotic drugs affects astroglial functions. Astroglial cells are involved in pH homeostasis of the brain by transporting protons (through sodium-proton transporter 1, NHE1, glutamate transporters EAAT1/2 and proton-lactate co-transporter MCT1) and bicarbonate (through the sodium-bicarbonate co-transporter NBC or the chloride-bicarbonate exchanger AE). Here we show that chronic treatment with fluoxetine increases astroglial pHi by stimulating NHE1-mediated proton extrusion. At a clinically relevant concentration of 1 μM, fluoxetine significantly increased astroglial pHi from 7.05 to 7.34 after 3 weeks and from 7.18 to 7.58 after 4 weeks of drug treatment. Stimulation of NHE1 is a result of transporter phosphorylation mediated by several intracellular signaling cascades that include MAPK/ERK1/2, PI3K/AKT and ribosomal S6 kinase (RSK). Fluoxetine stimulated phosphorylation of ERK1/2, AKT and RSK in a concentration dependent manner. Positive crosstalk exists between two signal pathways, MAPK/ERK1/2 and PI3K/AKT activated by fluoxetine since ERK1/2 phosphrylation could be abolished by inhibitors of PI3K, LY294002 and AKT, triciribine, and AKT phosphorylation by inhibitor of MAPK, U0126. As a result, RSK phosphorylation was not only inhibited by U0126 but also by inhibitor of LY294002. The NHE1 phoshorylation resulted in stimulation of NHE1 activity as revealed by the NH4Cl-prepulse technique; the increase of NHE1 activity was dependent on fluoxetine concentration, and could be inhibited by both U0126 and LY294002. Our findings suggest that regulation of astrocytic pHi and brain pH may be one of the mechanisms underlying fluoxetine action.
    Frontiers in Cellular Neuroscience 03/2015; 9:61. DOI:10.3389/fncel.2015.00061 · 4.29 Impact Factor
  • Source
    • "Ca2+ elevation represents a hallmark of cellular activation and has been shown to occur in astrocytes in response to neuronal activity (Verkhratsky and Kettenmann, 1996; Newman, 2003; Deitmer and Rose, 2010). Electrophysiology has been extensively used to impair Ca2+ signaling locally in populations of astrocytes through selective intracellular delivery of Ca2+ chelators contained in a patch pipette during whole cell recording of a single astrocyte. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A major breakthrough in neuroscience has been the realization in the last decades that the dogmatic view of astroglial cells as being merely fostering and buffering elements of the nervous system is simplistic. A wealth of investigations now shows that astrocytes actually participate in the control of synaptic transmission in an active manner. This was first hinted by the intimate contacts glial processes make with neurons, particularly at the synaptic level, and evidenced using electrophysiological and calcium imaging techniques. Calcium imaging has provided critical evidence demonstrating that astrocytic regulation of synaptic efficacy is not a passive phenomenon. However, given that cellular activation is not only represented by calcium signaling, it is also crucial to assess concomitant mechanisms. We and others have used electrophysiological techniques to simultaneously record neuronal and astrocytic activity, thus enabling the study of multiple ionic currents and in depth investigation of neuro-glial dialogues. In the current review, we focus on the input such approach has provided in the understanding of astrocyte-neuron interactions underlying control of synaptic efficacy.
    Frontiers in Cellular Neuroscience 10/2013; 7:159. DOI:10.3389/fncel.2013.00159 · 4.29 Impact Factor
Show more