Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia

Gergely Kovács, Zsuzsanna Környei, Krisztina Tóth, M. Baranyi, János Brunner, Máté Neubrandt, Ádám Dénes, B. Sperlágh

Research output: Contribution to journalArticle

Abstract

The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission. Changes in both P2X7R-mediated signaling and brain zinc homeostasis have been implicated in the pathogenesis of mood disorders. Here, we tested the hypothesis that extracellular zinc regulates P2X7R activity in the hippocampus. We observed that P2X7R is expressed in both neurons and glial cells in primary mouse hippocampal neuron-glia culture. Propidium iodide (PI) uptake through large pores formed by pannexins and P2X7R was dose-dependently inhibited by extracellular zinc ions. Calcium influx mediated by P2X7R in glial cells was also reduced by free zinc ions. Interestingly, no calcium influx was detected in response to ATP or 3′-O-(4-Benzoyl) benzoyl ATP (BzATP) in neurons despite the expression of P2X7R at the plasma membrane. Our results show that free zinc ions can modulate hippocampal glial purinergic signaling, and changes in the activity of P2X7R may contribute to the development of depression-like behaviors associated with zinc deficiency.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalCell Calcium
Volume75
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Purinergic P2X7 Receptors
Astrocytes
Zinc
Neuroglia
Neurons
Ions
Adenosine Triphosphate
Calcium
Purinergic P2 Receptors
Propidium
Synaptic Vesicles
Micronutrients
Brain
Mood Disorders
Synaptic Transmission
Cations
Hippocampus
Proteins
Homeostasis
Central Nervous System

Keywords

  • Glial cell
  • Hippocampus
  • Neuron
  • P2X7R
  • Purinergic receptor
  • Zinc

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia. / Kovács, Gergely; Környei, Zsuzsanna; Tóth, Krisztina; Baranyi, M.; Brunner, János; Neubrandt, Máté; Dénes, Ádám; Sperlágh, B.

In: Cell Calcium, Vol. 75, 01.11.2018, p. 1-13.

Research output: Contribution to journalArticle

Kovács, Gergely ; Környei, Zsuzsanna ; Tóth, Krisztina ; Baranyi, M. ; Brunner, János ; Neubrandt, Máté ; Dénes, Ádám ; Sperlágh, B. / Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia. In: Cell Calcium. 2018 ; Vol. 75. pp. 1-13.
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