TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases their proliferation

• Ohashi, Kana

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

• Deyashiki, Ayane

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

• Miyake, Takahito

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

• Nagayasu, Kazuki

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

• Shibasaki, Koji

  Department of Molecular and Cellular Neurology, Graduate School of Medicine, Gunma University

• Shirakawa, Hisashi

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

• Kaneko, Shuji

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

Abstract

Oligodendrocytes, which differentiate from oligodendrocyte precursor cells (OPCs), ensheath axons with myelin, play an essential role in rapid conduction of action potentials and metabolically support neurons. Elucidation of the mechanisms underlying the proliferation, migration, differentiation, and survival of OPCs is considered indispensable for determining the causes of central nervous system diseases. However, the relationship between these functions of OPCs and their intracellular Ca²⁺ signaling has not been fully elucidated. Here, we investigated the function of transient receptor potential vanilloid 4 (TRPV4), a Ca²⁺-permeable channel that responds to hypo-osmolarity, mild temperature, mechanical stimulation, and endogenous arachidonic acid metabolites, in OPCs. Trpv4 mRNA was detected in OPCs in vivo and in primary cultured rat OPCs. In Ca²⁺ imaging experiments, treatment with the selective TRPV4 agonist GSK1016790A induced sustained elevation of the intracellular Ca²⁺ concentration in OPCs in a concentration-dependent manner, which was almost completely suppressed by co-treatment with the selective TRPV4 antagonist HC067047. Stimulation of TRPV4 by GSK1016790A augmented OPC proliferation, which was abolished by co-treatment with HC067047, the intracellular Ca²⁺ chelator BAPTA-AM, and the protein kinase C inhibitor bisindolylmaleimide II. By contrast, GSK1016790A did not significantly affect the migration or differentiation of OPCs. Taken together, these results suggest that TRPV4 is functionally expressed in OPCs and increases the proliferation of these cells without affecting their ability to differentiate into oligodendrocytes.

This article is part of the special issue on Thermal biology in Pflügers Archiv – European Journal of Physiology.

Journal

• Pflügers Archiv - European Journal of Physiology

  Pflügers Archiv - European Journal of Physiology 470 (5), 705-716, 2018-05

  Springer

Keywords

• TRPV4 channel
• Oligodendrocyte precursor cells
• Ca²⁺ imaging
• Protein kinase C
• Cell proliferation

Details

• CRID: 1050006209983072128
• NII Article ID: 120007006244
• NII Book ID: AA00771833
• ISSN: 00316768
• ISSN: 14322013
• DOI: 10.1007/s00424-018-2130-3
• HANDLE: 2433/241626
• Web Site: http://link.springer.com/article/10.1007/s00424-018-2130-3/fulltext.html
• Web Site: http://link.springer.com/content/pdf/10.1007/s00424-018-2130-3.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN