The Ionic Mechanisms Regulating Astrocytic Calcium Dynamic

Dembitskaya Y.V., Lebedeva A.V., Pimashkin A.S., Semyanov A.V.

Key words: hippocampus; astrocytes; calcium oscillations; metabotropic glutamate receptors; neuron-glia interaction.

2016, volume 8, issue 4, page 191.

DOI: https://doi.org/10.17691/stm2016.8.4.24

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The aim of the study was to understand the effect of alterations in local ionic concentrations due to neuronal activity on calcium activity in astrocytes.

Materials and Methods. In this study we investigated astrocytic calcium dynamics using confocal microscopy on hippocampal slices from Wistar rats P15–18.

Results. Here we demonstrated that activation of metabotropic glutamate receptors on astrocytes led to an increase of the frequency and duration of calcium events. Elevations of the extracellular calcium concentration did not change the frequency and the duration. Elevations of the extracellular potassium concentration increased the frequency and reduced the duration of calcium events.

Conclusions. Neuronal activity causing alterations in local ionic concentrations might affect calcium activity in astrocytes, creating a feedback loop, controlling functioning of neuron-glia networks. These data indicate the complex nature of the effects, which modulate the interplay between neurons and astrocytes that cannot be considered only in the context of a receptor signaling.

Malarkey E.B., Parpura V. Mechanisms of glutamate release from astrocytes. Neurochem Int 2008; 52(1–2): 142–154, https://doi.org/10.1016/j.neuint.2007.06.005.
Verkhratsky A., Butt A. Glial neurobiology. Wiley-Blackwell; 2007, https://doi.org/10.1002/9780470517796.
Barres B.A. New roles for glia. J Neurosci 1991; 11(12): 3665–3694.
Haydon P.G. Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 2006; 86(3): 1009–1031, https://doi.org/10.1152/physrev.00049.2005.
Lebedeva A.V., Dembitskaya Y.V., Pimashkin A.S., Zhuravleva Z.D., Shishkova E.A., Semyanov A.V. The role of energy substrates in astrocyte calcium activity of rat hippocampus in early postnatal ontogenesis. Sovremennye tehnologii v medicine 2015; 7(3): 14–19, https://doi.org/10.17691/stm2015.7.3.02.
Agulhon C., Petravicz J., McMullen A.B., Sweger E.J., Minton S.K., Taves S.R., Casper K.B., Fiacco T.A., McCarthy K.D. What is the role of astrocyte calcium in neurophysiology? Neuron 2008; 59(6): 932–946, https://doi.org/10.1016/j.neuron.2008.09.004.
Finch E.A., Augustine G.J. Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature 1998; 396(6713): 753–756, https://doi.org/10.1038/25541.
Verkhratsky A. Glial calcium signaling in physiology and pathophysiology. Acta Pharmacol Sin 2006; 27(7): 773–780, https://doi.org/10.1111/j.1745-7254.2006.00396.x.
Cai Z., Schools G.P., Kimelberg H.K. Metabotropic glutamate receptors in acutely isolated hippocampal astrocytes: developmental changes of mGluR5 mRNA and functional expression. Glia 2000; 29(1): 70–80, https://doi.org/10.1002/(sici)1098-1136(20000101)29:170::aid-glia73.0.co;2-v.
Carlson M.D., Kish P.E., Ueda T. Characterization of the solubilized and reconstituted ATP-dependent vesicular glutamate uptake system. J Biol Chem 1989; 264(13): 7369–7376.
Koizumi S. Synchronization of Ca2+ oscillations: involvement of ATP release in astrocytes. FEBS J 2009; 277(2): 286–292, https://doi.org/10.1111/j.1742-4658.2009.07438.x.
Zur Nieden R. The role of metabotropic glutamate receptors for the generation of calcium oscillations in rat hippocampal astrocytes in situ. Cereb Cortex 2006; 16(5): 676–687, https://doi.org/10.1093/cercor/bhj013.
Bezzi P., Carmignoto G., Pasti L., Vesce S., Rossi D., Rizzini B.L., Pozzan T., Volterra A. Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 1998; 391(6664): 281–285, https://doi.org/10.1038/34651.
Petravicz J., Fiacco T.A., McCarthy K.D. Loss of IP3 receptor-dependent Ca2+ Increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J Neurosci 2008; 28(19): 4967–4973, https://doi.org/10.1523/jneu rosci.5572-07.2008.
Nedergaard M., Takano T., Hansen A.J. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 2002; 3(9): 748–755, https://doi.org/10.1038/nrn916.
Henneberger C., Papouin T., Oliet S.H.R., Rusakov D.A. Long-term potentiation depends on release of D-serine from astrocytes. Nature 2010; 463(7278): 232–236, https://doi.org/10.1038/nature08673.
Fellin T., Pascual O., Gobbo S., Pozzan T., Haydon P.G., Carmignoto G. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 2004; 43(5): 729–743, https://doi.org/10.1016/j.neuron.2004.08.011.
Berridge M.J. Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 2009; 1793(6): 933–940, https://doi.org/10.1016/j.bbamcr.2008.10.005.
De Pittà M., Goldberg M., Volman V., Berry H., Ben-Jacob E. Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes. J Biol Phys 2009; 35(4): 383–411, https://doi.org/10.1007/s10867-009-9155-y.
Keizer J., Li Y.X., Stojilkovic S., Rinzel J. InsP3-induced Ca2+ excitability of the endoplasmic reticulum. Mol Biol Cell 1995; 6(8): 945–951, https://doi.org/10.1091/mbc.6.8.945.
Chen K.C., Nicholson C. Spatial buffering of potassium ions in brain extracellular space. Biophys J 2000; 78(6): 2776–2797, https://doi.org/10.1016/s0006-3495(00)76822-6.
DiChiara T.J., Reinhart P.H. Distinct effects of Ca2+ and voltage on the activation and deactivation of cloned Ca2+-activated K+ channels. J Physiol 1995; 489(2): 403–418, https://doi.org/10.1113/jphysiol.1995.sp021061.
Janigro D., Gasparini S., D’Ambrosio R., McKhann G. 2nd, DiFrancesco D. Reduction of K+ uptake in glia prevents long-term depression maintenance and causes epileptiform activity. J Neurosci 1997; 17(8): 2813–2824.
Sem’ianov A.V. Glutamate- and GABA-mediated extrasynaptic diffuse signaling in the hippocampus. Zh Vyssh Nerv Deiat Im I P Pavlova 2004; 54(1): 68–84.
Leybaert L., Cabooter L., Braet K. Calcium signal communication between glial and vascular brain cells. Acta Neurol Belg 2004; 104(2): 51–56.
Fields R.D., Ni Y. Nonsynaptic communication through ATP release from volume-activated anion channels in axons. Sci Signal 2010; 3(142): ra73, https://doi.org/10.1126/scisignal.2001128.
Hamilton N.B., Attwell D. Do astrocytes really exocytose neurotransmitters? Nat Rev Neurosci 2010; 11(4): 227–238, https://doi.org/10.1038/nrn2803.
Meeks J.P., Mennerick S. Astrocyte membrane responses and potassium accumulation during neuronal activity. Hippocampus 2007; 17(11): 1100–1108, https://doi.org/10.1002/hipo.20344.
Shih P.-Y., Savtchenko L.P., Kamasawa N., Dembitskaya Y., McHugh T.J., Rusakov D.A., Shigemoto R., Semyanov A. Retrograde synaptic signaling mediated by K+ efflux through postsynaptic NMDA receptors. Cell Rep 2013; 5(4): 941–951, http://doi.org/10.1016/j.celrep.2013.10.026.