Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

Takanori Shinotsuka, Masato Yasui, Mutsuo Nuriya

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca2+]i) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca2+]i oscillations followed by larger and sustained [Ca2+]i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca2+]i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca2+]i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca2+]i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume444
Issue number2
DOIs
Publication statusPublished - 2014 Feb 7

Keywords

  • Anoxic depolarization
  • Astrocyte
  • Calcium
  • Gap junction
  • Two-photon microscopy

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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