Axon initial segment Ca2+ channels influence action potential generation and timing

Neuron. 2009 Jan 29;61(2):259-71. doi: 10.1016/j.neuron.2008.12.004.


Although action potentials are typically generated in the axon initial segment (AIS), the timing and pattern of action potentials are thought to depend on inward current originating in somatodendritic compartments. Using two-photon imaging, we show that T- and R-type voltage-gated Ca(2+) channels are colocalized with Na(+) channels in the AIS of dorsal cochlear nucleus interneurons and that activation of these Ca(2+) channels is essential to the generation and timing of action potential bursts known as complex spikes. During complex spikes, where Na(+)-mediated spikelets fire atop slower depolarizing conductances, selective block of AIS Ca(2+) channels delays spike timing and raises spike threshold. Furthermore, AIS Ca(2+) channel block can decrease the number of spikelets within a complex spike and can even block single, simple spikes. Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca(2+) channels at the site of spike initiation play a key role in generating and shaping spike bursts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / metabolism*
  • Axons / ultrastructure
  • Calcium Channels / metabolism*
  • Calcium Channels, R-Type / metabolism
  • Calcium Channels, T-Type / metabolism
  • Calcium Signaling / physiology*
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Cochlear Nucleus / cytology
  • Cochlear Nucleus / metabolism*
  • Ion Channel Gating / physiology
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Sodium Channels / metabolism
  • Time Factors


  • Calcium Channels
  • Calcium Channels, R-Type
  • Calcium Channels, T-Type
  • Sodium Channels