Activation of the melastatin-related cation channel TRPM3 by D-erythro-sphingosine [corrected]

Mol Pharmacol. 2005 Mar;67(3):798-805. doi: 10.1124/mol.104.006734. Epub 2004 Nov 18.


TRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain. TRPM3 mediates spontaneous Ca2+ entry and nonselective cation currents in transiently transfected human embryonic kidney 293 cells. Using measurements with the Ca2+-sensitive fluorescent dye fura-2 and the whole-cell patch-clamp technique, we found that D-erythro-sphingosine, a metabolite arising during the de novo synthesis of cellular sphingolipids, activated TRPM3. Other transient receptor potential (TRP) channels tested [classic or canonical TRP (TRPC3, TRPC4, TRPC5), vanilloid-like TRP (TRPV4, TRPV5, TRPV6), and melastatin-like TRP (TRPM2)] did not significantly respond to application of sphingosine. Sphingosine-induced TRPM3 activation was not mediated by inhibition of protein kinase C, depletion of intracellular Ca2+ stores, and intracellular conversion of sphingosine to sphingosine-1-phosphate. Although sphingosine-1-phosphate and ceramides had no effect, two structural analogs of sphingosine, dihydro-D-erythro-sphingosine and N,N-dimethyl-D-erythro-sphingosine, also activated TRPM3. Sphingolipids, including sphingosine, are known to have inhibitory effects on a variety of ion channels. Thus, TRPM3 is the first ion channel activated by sphingolipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Line
  • Humans
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Kidney
  • Kinetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Recombinant Proteins / metabolism
  • Sphingolipids / pharmacology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*
  • TRPM Cation Channels
  • Transfection


  • Ion Channels
  • Recombinant Proteins
  • Sphingolipids
  • TRPM Cation Channels
  • TRPM3 protein, human
  • erythro-(2R,3S)-sphingosine
  • Sphingosine
  • Calcium