Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones

Nature. 2005 Apr 14;434(7035):898-904. doi: 10.1038/nature03478. Epub 2005 Mar 9.


Ion channels formed by the TRP (transient receptor potential) superfamily of proteins act as sensors for temperature, osmolarity, mechanical stress and taste. The growth cones of developing axons are responsible for sensing extracellular guidance factors, many of which trigger Ca2+ influx at the growth cone; however, the identity of the ion channels involved remains to be clarified. Here, we report that TRP-like channel activity exists in the growth cones of cultured Xenopus neurons and can be modulated by exposure to netrin-1 and brain-derived neurotrophic factor, two chemoattractants for axon guidance. Whole-cell recording from growth cones showed that netrin-1 induced a membrane depolarization, part of which remained after all major voltage-dependent channels were blocked. Furthermore, the membrane depolarization was sensitive to blockers of TRP channels. Pharmacological blockade of putative TRP currents or downregulation of Xenopus TRP-1 (xTRPC1) expression with a specific morpholino oligonucleotide abolished the growth-cone turning and Ca2+ elevation induced by a netrin-1 gradient. Thus, TRPC currents reflect early events in the growth cone's detection of some extracellular guidance signals, resulting in membrane depolarization and cytoplasmic Ca2+ elevation that mediates the turning of growth cones.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / deficiency
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / drug effects
  • Cell Movement / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Electric Conductivity
  • Growth Cones / drug effects*
  • Growth Cones / metabolism
  • Imidazoles / pharmacology
  • Membrane Potentials / drug effects
  • Nerve Growth Factors / pharmacology*
  • Netrin-1
  • TRPC Cation Channels
  • Tumor Suppressor Proteins
  • Xenopus laevis / embryology


  • Brain-Derived Neurotrophic Factor
  • Calcium Channel Blockers
  • Calcium Channels
  • Imidazoles
  • Nerve Growth Factors
  • TRPC Cation Channels
  • Tumor Suppressor Proteins
  • transient receptor potential cation channel, subfamily C, member 1
  • Netrin-1
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium