Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia

Nörenberg, Wolfgang; Schunk, Jessica; Fischer, Wolfgang B.; Sobottka, Helga; Riedel, Thomas; Oliveira, João Filipe; Franke, Heike; Illéš, Peter

doi:10.1111/j.1476-5381.2010.00736.x

Cited by 50 publications

(34 citation statements)

References 52 publications

(105 reference statements)

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“…The inward current is carried by Na + and Ca 2+ ions, the latter of which being responsible for the [Ca 2+ ] i increase (Sperlágh et al 2006;Skaper et al 2010). The (partial) sensitivity of the astroglial Bz-ATP current to blockade by selective P2X7 receptor antagonists in a low X 2+ medium has been documented repeatedly (Nörenberg et al 2010;Oliveira et al 2011;Messemer et al 2013) and was, therefore, not studied in the present experiments.…”

Section: Resultsmentioning

confidence: 86%

“…Absence of P2X7 receptors at cultured hippocampal neurons, but not astrocytes: a Ca 2+ -imaging study Most astrocytes formed a confluent layer of flat cells, which were devoid of clearly circumscribable borders and appendages (for cortical cell cultures, see Nörenberg et al 2010). Neurons and a subgroup of astrocytes grew on the surface of the astrocytic carpet or apart of it; they had clear cell boundaries and numerous cellular processes.…”

Section: Resultsmentioning

confidence: 99%

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Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Rubini

Pagel

Mehri

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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P2X7 receptors have been suggested to be located both on neurons and astrocytes of the central and peripheral nervous systems. In the present Ca(2+)-imaging and patch-clamp study, we reinvestigated these findings on mixed neuronal-astrocytic cell cultures prepared from embryonic or newborn rat hippocampi. We found in a Mg(2+)-free bath medium that the prototypic P2X7 receptor agonist dibenzoyl-adenosine triphosphate (Bz-ATP) increased the intracellular Ca(2+) concentration ([Ca(2+)]i) both in the neuronal cell bodies and in their axo-dendritic processes only to a very minor extent. However, Bz-ATP produced marked [Ca(2+)]i transients in the neuronal processes, when they grew above a glial carpet, which was uniformly sensitive to Bz-ATP. These glial signals might be misinterpreted as neuronal responses because of the poor focal discrimination by a fluorescent microscope. Most astrocytes had a polygonal shape without clearly circumscribable boundaries, but a subgroup of them had neuron-like appearance. The cellular processes of this astrocytic subgroup, just as their cell somata and their polygonal counterparts, appeared to possess a high density of functional P2X7 receptors. In contrast to astrocytes, in a low Ca(2+)/no Mg(2+)-containing bath medium, hippocampal neurons failed to respond to Bz-ATP with membrane currents. In addition, neither the amplitude nor the frequency of spontaneous excitatory postsynaptic currents, representing the quantal release of glutamate, was modified by Bz-ATP. We conclude that cultured hippocampal neurons, in contrast to astrocytes, possess P2X7 receptors, if at all, only at a low density.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Rubini

Pagel

Mehri

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In mouse cerebellar astrocytes, nondesensitizing currents were elicited by the two nucleotides, and, as expected, BzATP displayed higher potency than ATP (Duan et al, 2003;Nörenberg et al, 2010Nörenberg et al, , 2011. The magnitude and the current density of BzATP-induced currents in mouse cerebellar astrocytes (approximately 30 pA/pF) were much higher than those from rat cerebellar astrocytes (approximately 3 pA/pF) (Carrasquero et al, 2009).…”

Section: Discussionmentioning

confidence: 91%

“…6A). Currents evoked by 1 mM ATP were less than half (72.85 6 21.2 pA; n 5 9 cells) of those activated by BzATP in the same cells (171.90 6 36.47 pA), suggesting a lower potency of the endogenous agonist at this ionotropic purinergic receptor (Young et al, 2008;Nörenberg et al, 2010;Oliveira et al, 2011). Peak currents evoked by BzATP in the entire group of cells tested were of 170.11 6 18.30 pA (n 5 42 cells), which considering an average membrane capacitance of 16.8 6 0.9 pF, implies a mean current density of approximately 10 pA/pF.…”

Section: P2x7 Receptors Mediate Membrane Current Responses Evoked By mentioning

confidence: 99%

Purinergic P2X7 Receptors Mediate Cell Death in Mouse Cerebellar Astrocytes in Culture

Salas

Carrasquero

Olivos-Oré

et al. 2013

J Pharmacol Exp Ther

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The brain distribution and functional role of glial P2X7 receptors are broader and more complex than initially anticipated. We characterized P2X7 receptors from cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding for P2X7 receptors, which is translated into P2X7 receptor protein as proven by Western blot analysis and immunocytochemistry. Fura-2 imaging showed cytosolic calcium responses to ATP and the synthetic analog 39-O-(4-benzoyl)benzoyl-ATP (BzATP) exhibited two components, namely an initial transient and metabotropic component followed by a sustained one that depended on extracellular calcium. This latter component, which was absent in astrocytes from P2X7 receptor knockout mice (P2X7 KO), was modulated by extracellular Mg 21, and was sensitive to Brilliant Blue G (BBG) and 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine (A438079) antagonism. BzATP also elicited inwardly directed nondesensitizing whole-cell ionic currents that were reduced by extracellular Mg 21 and P2X7 antagonists (BBG and calmidazolium). In contrast to that previously reported in rat cerebellar astrocytes, sustained BzATP application induced a gradual increase in membrane permeability to large cations, such as N-methyl-D-glucamine and 4-[3-methyl-2(3H)-benzoxazolylidene)-methyl]-1-[3-(triethylammonio)propyl]diiodide, which ultimately led to the death of mouse astrocytes. Cerebellar astrocyte cell death was prevented by BBG but not by calmidazolium, removal of extracellular calcium, or treatment with the caspase-3 inhibitor, benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, thus suggesting a necrotictype mechanism of cell death. Since this cellular response was not observed in astrocytes from P2X7 KO mice, this study suggests that stimulation of P2X7 receptor may convey a cell death signal to cerebellar astrocytes in a species-specific manner.

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“…Astrocytes were also reported to express functional P2X 7 receptors, which were identifi ed in freshly isolated human retinal Müller cells (Pannicke et al 2000 ), in cultured astrocytes (Duan et al 2003 ;Norenberg et al 2010 ) and in cortical and hippocampal astrocytes in situ in acute brain slices (Fellin et al 2006 ;Oliveira et al 2011 ). The role of P2X 7 receptors in astroglial physiology remains speculative, although they may be important for pathological reactions of astroglia Illes et al 2012 ).…”

Section: Ionotropic P2x Purinoceptorsmentioning

confidence: 97%

Purinergic and Glutamatergic Receptors on Astroglia

Verkhratsky

Burnstock

2014

Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain

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Astroglial cells express many neurotransmitter receptors; the receptors to glutamate and ATP being the most abundant. Here, we provide a concise overview on the expression and main properties of astroglial glutamate receptors (ionotropic receptors represented by AMPA and NMDA subtypes) and metabotropic (mainly mGluR5 and mGluR3 subtypes) and purinoceptors (adenosine receptors of A1, A2A, A2B, and A3 types, ionotropic P2X1/5 and P2X7 subtypes, and metabotropic P2Y purinoceptors). We also discuss the role of these receptors in glial physiology and pathophysiology.

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Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia

Cited by 50 publications

References 52 publications

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Purinergic P2X7 Receptors Mediate Cell Death in Mouse Cerebellar Astrocytes in Culture

Purinergic and Glutamatergic Receptors on Astroglia

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