IGF-1 modulates N and L calcium channels in a PI 3-kinase-dependent manner

Neuron. 1997 Aug;19(2):421-9. doi: 10.1016/s0896-6273(00)80950-2.


Receptor tyrosine kinases (RTKs) have long been associated with proliferation in non-neural cells, although they are also expressed in postmitotic neurons. We demonstrate that insulin-like growth factor-1 (IGF-1) induces within seconds a large, tyrosine-kinase-dependent increase in calcium channel currents in cerebellar granule neurons. Separation of channel subtypes reveals that, while P, Q, and R channels are unaffected, N and L channel activities are strongly potentiated at specific membrane voltages: N currents triple at depolarized potentials, while L currents rapidly increase 4-fold at hyperpolarized potentials. Moreover, transient expression of dominant-negative and wild-type phosphatidylinositol 3-OH kinase (PI 3-kinase) subunits, as well as application of specific inhibitors, demonstrates that PI 3-kinase is an essential and rate-limiting messenger in this signaling pathway. Our results indicate that N and L calcium channels are downstream targets of neuronal RTKs and suggest that RTK modulation may control calcium-dependent processes, such as neurotransmitter release and IGF-1-dependent differentiation or survival.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Cells, Cultured
  • Cerebellum / drug effects
  • Insulin-Like Growth Factor I / pharmacology*
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / physiology*
  • Rats


  • Calcium Channels
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)