Direct posttranslational modification of astrocytic connexin 43 proteins by the general anesthetic propofol in the cerebral cortex

Mutsuo Nuriya, Daisuke Yasui, Tomoko Yamada, Takuma Aoki, Masato Yasui

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Propofol is widely used as a general anesthetic and is generally considered to exert its action by regulating neuronal firing via facilitation of GABAA receptors. However, accumulating evidence suggests that propofol also acts on astrocytes, including inhibitory effects on gap junctional coupling, but the underlying molecular mechanisms remain largely unknown. Here, using acute cortical brain slices prepared from mice, we characterize propofol-induced molecular changes in astrocytic gap junction protein connexin 43 (Cx43). Propofol does not change the protein expression level of Cx43 or its incorporation into gap junctional plaques, according to biochemical and immunohistochemical analyses. However, propofol alters migration pattern of Cx43 on western blot, suggesting changes in its posttranslational modifications. Indeed, this change is accompanied by an increase in the phosphorylation of Cx43 at serine 368, which is known to reduce permeability of Cx43 gap junctions. Finally, we show that this change occurs in the absence of neuronal firing or glutamatergic transmissions. Overall, these results show that propofol induces posttranslational modification of Cx43 directly on astrocytes at the site of gap junctional plaques, exerting direct pharmacological action on astrocytes in parallel with its action on neurons.

本文言語English
ページ(範囲)734-741
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
497
2
DOI
出版ステータスPublished - 2018 3月 4

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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