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

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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.

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Acknowledgments

We appreciate Dr. H. Takebayashi (Niigata Univ.) for the generous gift of PDGFRα, plp, and gfap ISH plasmids, and Dr. K. Arai (Harvard Univ.) for his excellent advice on primary culture of oligodendrocyte precursor cells.

Funding

This work was supported by MEXT/JSPS KAKENHI Grant Numbers 17K19486 (to H.S.), 24390016 (to S.K.), JP15H05934 <Thermal Biology> (to K.S.), and JP15H03000 (to K.S.), and also supported by the Takeda Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to H.S.)

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  1. Kana Ohashi and Ayane Deyashiki contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Kana Ohashi, Ayane Deyashiki, Takahito Miyake, Kazuki Nagayasu, Hisashi Shirakawa & Shuji Kaneko

  2. Department of Molecular and Cellular Neurology, Graduate School of Medicine, Gunma University, Maebashi, 371-8511, Japan

    Koji Shibasaki

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  1. Kana Ohashi
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Correspondence to Hisashi Shirakawa.

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All experiments were conducted in accordance with the ethical guidelines set down by the Kyoto University Animal Research Committee.

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

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Ohashi, K., Deyashiki, A., Miyake, T. et al. TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases their proliferation. Pflugers Arch - Eur J Physiol 470, 705–716 (2018). https://doi.org/10.1007/s00424-018-2130-3

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