Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels

J Physiol. 2008 Dec 1;586(23):5633-49. doi: 10.1113/jphysiol.2008.161257. Epub 2008 Oct 2.


Transient receptor potential (TRP) channels mediate a wide array of sensory functions. We investigated the role of TRPC5, a poorly characterized channel widely expressed in the central and peripheral nervous system, as a potential osmosensory protein. Here we show that hypoosmotic stimulation activates TRPC5 channels resulting in a large calcium influx. The response to osmotically induced membrane stretch is blocked by GsMTx-4, an inhibitor of stretch activated ion channels. Direct hypoosmotic activation of TRPC5 is independent of phospholipase C function. However, the osmotic response is inhibited in a cell line in which PIP(2) levels are reduced by regulated overexpression of a lipid phosphatase. The response was restored by increasing intracellular PIP(2) levels through the patch pipette. The mechano-sensitivity of the channel was probed in the whole-cell configuration by application of steps of positive pressure through the patch pipette. Pressure-induced membrane stretch also activated TRPC5 channels, suggesting its role as a transducer of osmo-mechanical stimuli. We also demonstrated the expression of TRPC5 in sensory neurones which together with the osmo-mechanical characteristics of TRPC5 channels suggest its putative role in mechanosensory transduction events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Cell Line
  • Cell Membrane / physiology*
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Estrenes / pharmacology
  • Ganglia, Spinal / metabolism
  • Hippocampus / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Osmotic Pressure
  • Peptides / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Pressure
  • Pyrrolidinones / pharmacology
  • Sensory Receptor Cells / metabolism
  • Spider Venoms / pharmacology
  • Stress, Mechanical
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / physiology*
  • Thapsigargin / pharmacology
  • Transfection
  • Trigeminal Ganglion / metabolism
  • Type C Phospholipases / antagonists & inhibitors


  • Estrenes
  • Intercellular Signaling Peptides and Proteins
  • MTx4 protein, Grammostola spatulata
  • Peptides
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Spider Venoms
  • TRPC Cation Channels
  • Trpc5 protein, mouse
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Thapsigargin
  • Carbachol
  • Phosphoric Monoester Hydrolases
  • phosphoinositide 5-phosphatase
  • Type C Phospholipases
  • Calcium