Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1

Pflugers Arch. 2007 Dec;455(3):465-77. doi: 10.1007/s00424-007-0314-3. Epub 2007 Jul 24.


Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca(2+) stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1(-/-) mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1(-/-) mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1(-/-) mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta, Thoracic / cytology
  • Base Sequence
  • Calcium Channels
  • Cerebral Arteries / cytology
  • Indoles / pharmacology
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • RNA, Small Interfering / pharmacology
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels / deficiency
  • TRPC Cation Channels / physiology*
  • Thapsigargin / pharmacology


  • Calcium Channels
  • Indoles
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • Thapsigargin
  • Inositol 1,4,5-Trisphosphate
  • cyclopiazonic acid