Depletion of intracellular Ca2+ stores stimulates the translocation of vanilloid transient receptor potential 4-c1 heteromeric channels to the plasma membrane

Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2249-55. doi: 10.1161/ATVBAHA.110.212084. Epub 2010 Aug 12.


Objective: To examine the effect of Ca(2+) store depletion on the translocation of vanilloid transient receptor potential (TRPV) 4-C1 heteromeric channels to the plasma membrane.

Methods and results: Vesicular trafficking is a key mechanism for controlling the surface expression of TRP channels in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. Experiments using total internal fluorescence reflection microscopy and biotin surface labeling show that Ca(2+) store depletion enhanced TRPV4-C1 translocation into the plasma membrane in human embryonic kidney 293 cells that were coexpressed with TRPV4 and canonical transient receptor potential 1 (TRPC1). Fluorescent Ca(2+) measurement and patch clamp studies demonstrated that Ca(2+) store depletion enhanced 4α-PDD-stimulated Ca(2+) influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). TRPV4-C1 heteromeric channels were more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomeric channels. Similar results were obtained in native vascular endothelial cells.

Conclusions: Ca(2+) store depletion stimulates the insertion of TRPV4-C1 heteromeric channels into the plasma membrane, resulting in an augmented Ca(2+) influx in response to flow in the human embryonic kidney cell overexpression system and native endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Membrane / physiology*
  • Cells, Cultured
  • Cytoplasmic Vesicles / physiology
  • Endothelial Cells
  • HEK293 Cells
  • Humans
  • Patch-Clamp Techniques
  • TRPV Cation Channels / physiology*
  • Umbilical Veins / cytology


  • TRPV Cation Channels
  • TRPV4 protein, human
  • Calcium