TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells

Am J Physiol Cell Physiol. 2007 Jan;292(1):C460-7. doi: 10.1152/ajpcell.00367.2006. Epub 2006 Aug 30.

Abstract

Stretch- and swelling-activated cation (SSAC) channels play essential roles not only in sensing and transducing external mechanical stresses but also in regulating cell volume in living cells. However, the molecular nature of the SSAC channel has not been clarified. In human epithelial HeLa cells, single-channel recordings in cell-attached and inside-out patches revealed expression of a Mg(2+)- and Gd(3+)-sensitive nonselective cation channel that is exquisitely sensitive to membrane stretch. Whole cell recordings revealed that the macroscopic cationic currents exhibit transient receptor potential (TRP) melastatin (TRPM)7-like properties such as outward rectification and sensitivity to Mg(2+) and Gd(3+). The whole cell cation current was augmented by osmotic cell swelling. RT-PCR and Western blotting demonstrated molecular expression of TRPM7 in HeLa cells. Treatment with small interfering RNA (siRNA) targeted against TRPM7 led to abolition of single stretch-activated cation channel currents and of swelling-activated, whole cell cation currents in HeLa cells. The silencing of TRPM7 by siRNA reduced the rate of cell volume recovery after osmotic swelling. A similar inhibition of regulatory volume decrease was also observed when extracellular Ca(2+) was removed or Gd(3+) was applied. It is thus concluded that TRPM7 represents the SSAC channel endogenously expressed in HeLa cells and that, by serving as a swelling-induced Ca(2+) influx pathway, it plays an important role in cell volume regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Size*
  • Electric Conductivity
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Gadolinium / pharmacology
  • Humans
  • Magnesium / pharmacology
  • Osmosis
  • Physical Stimulation
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering / pharmacology
  • Ruthenium Red / pharmacology
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / drug effects
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / physiology*

Substances

  • RNA, Small Interfering
  • TRPM Cation Channels
  • Ruthenium Red
  • Gadolinium
  • Protein-Serine-Threonine Kinases
  • TRPM7 protein, human
  • Magnesium