Affordable Access

Access to the full text

TRPM7 channel activity in Jurkat T lymphocytes during magnesium depletion and loading: implications for divalent metal entry and cytotoxicity

Authors
  • Mellott, Alayna1
  • Rockwood, Jananie1
  • Zhelay, Tetyana1
  • Luu, Charles Tuan1
  • Kaitsuka, Taku2
  • Kozak, J. Ashot1
  • 1 Wright State University, Dayton, OH, 45435, USA , Dayton (United States)
  • 2 International University of Health and Welfare, Enokizu 137-1, Okawa, Fukuoka, Japan , Fukuoka (Japan)
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Sep 22, 2020
Volume
472
Issue
11
Pages
1589–1606
Identifiers
DOI: 10.1007/s00424-020-02457-3
Source
Springer Nature
Keywords
License
Yellow

Abstract

TRPM7 is a cation channel-protein kinase highly expressed in T lymphocytes and other immune cells. It has been proposed to constitute a cellular entry pathway for Mg2+ and divalent metal cations such as Ca2+, Zn2+, Cd2+, Mn2+, and Ni2+. TRPM7 channels are inhibited by cytosolic Mg2+, rendering them largely inactive in intact cells. The dependence of channel activity on extracellular Mg2+ is less well studied. Here, we measured native TRPM7 channel activity in Jurkat T cells maintained in external Mg2+ concentrations varying between 400 nM and 1.4 mM for 1–3 days, obtaining an IC50 value of 54 μM. Maintaining the cells in 400 nM or 8 μM [Mg2+]o resulted in almost complete activation of TRPM7 in intact cells, due to cytosolic Mg2+ depletion. A total of 1.4 mM [Mg2+]o was sufficient to fully eliminate the basal current. Submillimolar concentrations of amiloride prevented cellular Mg2+ depletion but not loading. We investigated whether the cytotoxicity of TRPM7 permeant metal ions Ni2+, Zn2+, Cd2+, Co2+, Mn2+, Sr2+, and Ba2+ requires TRPM7 channel activity. Mg2+ loading modestly reduced cytotoxicity of Zn2+, Co2+, Ni2+, and Mn2+ but not of Cd2+. Channel blocker NS8593 reduced Co2+ and Mn2+ but not Cd2+ or Zn2+ cytotoxicity and interfered with Mg2+ loading as evaluated by TRPM7 channel basal activity. Ba2+ and Sr2+ were neither detectably toxic nor permeant through the plasma membrane. These results indicate that in Jurkat T cells, entry of toxic divalent metal cations primarily occurs through pathways distinct from TRPM7. By contrast, we found evidence that Mg2+ entry requires TRPM7 channels.

Report this publication

Statistics

Seen <100 times