Insulin-like growth factor I modifies electrophysiological properties of rat brain stem neurons

J Neurophysiol. 2003 Jun;89(6):3008-17. doi: 10.1152/jn.00089.2003. Epub 2003 Feb 5.


On systemic injection, insulin-like growth factor I (IGF-I) elicits a prolonged increase in the excitability of dorsal column nuclei (DCN) cells in the brain stem as well as other target neurons within the brain. We have explored the cellular mechanisms involved in the stimulatory effects of IGF-I as well as its functional consequences. In a rat slice preparation, IGF-I induced a sustained depolarization of 2-5 mV in 81% of DCN neurons. Depolarization was accompanied with an increase in the input resistance (15%). Voltage-clamp recordings displayed that IGF-I decreased a K+-mediated A current (60%). Furthermore, IGF-I increased, in 78% of cells, the peak amplitude (25%), and rising slope (32%) of the excitatory postsynaptic potential evoked by dorsal column stimulation; in this case, a presynaptic facilitatory process appears to be involved. When anesthetized adult rats are injected in the carotid artery with IGF-I, extracellularly recorded propioceptive DCN neurons not only show increased spike activity but also an expansion of their cutaneous receptive field in 83% of DCN cells. Significantly, the increased excitability evoked by IGF-I in the DCN cells depends both in vivo and in vitro, on activation of p38 mitogen-activated protein kinase (MAPK), a Ser-kinase known to modulate K+ channel activity. We concluded that systemic IGF-I modulated the electrophysiological properties of target neurons within the brain. In turn, these changes probably contribute to functional reorganization processes such as expansion of neuronal receptive fields.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials
  • Animals
  • Brain Stem / cytology
  • Brain Stem / drug effects
  • Brain Stem / physiology*
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor I / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Posterior Horn Cells / physiology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / physiology
  • Rats
  • Rats, Wistar
  • Synaptic Transmission* / drug effects
  • p38 Mitogen-Activated Protein Kinases


  • Enzyme Inhibitors
  • Flavonoids
  • Potassium Channel Blockers
  • Potassium Channels
  • Insulin-Like Growth Factor I
  • 4-Aminopyridine
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one