Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement

Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2012894118. doi: 10.1073/pnas.2012894118.

Abstract

Microglia maintain central nervous system homeostasis by monitoring changes in their environment (resting state) and by taking protective actions to equilibrate such changes (activated state). These surveillance and protective roles both require constant movement of microglia. Interestingly, induced hypothermia can reduce microglia migration caused by ischemia, suggesting that microglia movement can be modulated by temperature. Although several ion channels and transporters are known to support microglia movement, the precise molecular mechanism that regulates temperature-dependent movement of microglia remains unclear. Some members of the transient receptor potential (TRP) channel superfamily exhibit thermosensitivity and thus are strong candidates for mediation of this phenomenon. Here, we demonstrate that mouse microglia exhibit temperature-dependent movement in vitro and in vivo that is mediated by TRPV4 channels within the physiological range of body temperature. Our findings may provide a basis for future research into the potential clinical application of temperature regulation to preserve cell function via manipulation of ion channel activity.

Keywords: TRP channels; TRPV4; microglia; movement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cells, Cultured
  • Central Nervous System / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Signal Transduction
  • TRPV Cation Channels / metabolism*
  • TRPV Cation Channels / physiology
  • Temperature
  • Transient Receptor Potential Channels / metabolism

Substances

  • TRPV Cation Channels
  • Transient Receptor Potential Channels
  • Trpv4 protein, mouse