Pathophysiological Roles of Transient Receptor Potential Channels in Glial Cells

• SHIRAKAWA Hisashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• NAKAGAWA Takayuki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• KANEKO Shuji

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

Bibliographic Information

Other Title

• 脳内グリア細胞におけるtransient receptor potential channelの病態生理的役割
• ノウナイ グリア サイボウ ニ オケル transient receptor potential channel ノ ビョウタイ セイリテキ ヤクワリ

Abstract

  Glial cells are abundant in the CNS and play diverse roles in the regulation of neuronal activity, vascular function, and gliotransmitter release, whereas pathologically activated glial cells have been reported to disturb brain function in conjunction with Ca²⁺ signaling, however there is no enough explanation for a unique Ca²⁺ entry. Transient receptor potential (TRP) superfamily comprises a group of non-selective cation channels that open in response to divergent stimuli in their environment. Although TRP channels are widely distributed in the mammalian brain, their roles remain to be elucidated. Here we provide an overview of the roles of TRP channels in pathophysiological processes, especially focusing on TRPC3 and TRPV4 channels in glial cells. Using rat cortical astrocytes, we found that TRPC3 was upregulated by thrombin via Ca²⁺ signaling through TRPC3 itself. Thrombin also upregulated S100B, a marker of reactive astrocytes, and increased cell proliferation, both of which were inhibited by Ca²⁺ signaling blockers and specific knockdown of TRPC3 using siRNA, suggesting that TRPC3 contributes to the pathological activation of astrocytes in part through a feed-forward upregulation of its own expression. Moreover, we found that TRPV4 stimulation by its agonist 4α-PDD suppressed LPS-induced microglial activation while TRPV4 mRNA was downregulated in LPS-treated cultured rat microglia. These results suggest that TRP channels play pivotal roles in the process of astrocytic and microglial activation.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 130 (3), 281-287, 2010-03-01

  The Pharmaceutical Society of Japan

Keywords

• transient receptor potential (TRP) channel
• Ca²⁺ mobilization
• astrocytes
• thrombin
• microglia
• lipopolysaccharide

Details

• CRID: 1390282681104615808
• NII Article ID: 130000259509
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.130.281
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 10588200
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10588200
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/130/3/130_3_281/_pdf
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed