Neurotrophin-evoked rapid excitation through TrkB receptors

Nature. 1999 Oct 28;401(6756):918-21. doi: 10.1038/44847.


Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. They are also essential for modulating activity-dependent neuronal plasticity. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Brain-Derived Neurotrophic Factor / physiology
  • Calcium / metabolism
  • Carbazoles / pharmacology
  • Glutamic Acid / physiology
  • In Vitro Techniques
  • Indole Alkaloids
  • Membrane Potentials
  • Nerve Growth Factors / physiology*
  • Neurotransmitter Agents / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Wistar
  • Receptor, trkB / physiology*
  • Sodium Channels / physiology
  • Synaptic Transmission / physiology*


  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • Indole Alkaloids
  • Nerve Growth Factors
  • Neurotransmitter Agents
  • Sodium Channels
  • Glutamic Acid
  • staurosporine aglycone
  • Receptor, trkB
  • Calcium