Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation

Neuron. 2010 Nov 4;68(3):500-11. doi: 10.1016/j.neuron.2010.09.026.


Action potentials initiate in the axon initial segment (AIS), a specialized compartment enriched with Na(+) and K(+) channels. Recently, we found that T- and R-type Ca(2+) channels are concentrated in the AIS, where they contribute to local subthreshold membrane depolarization and thereby influence action potential initiation. While periods of high-frequency activity can alter availability of AIS voltage-gated channels, mechanisms for long-term modulation of AIS channel function remain unknown. Here, we examined the regulatory pathways that control AIS Ca(2+) channel activity in brainstem interneurons. T-type Ca(2+) channels were downregulated by dopamine receptor activation acting via protein kinase C, which in turn reduced neuronal output. These effects occurred without altering AIS Na(+) or somatodendritic T-type channel activity and could be mediated by endogenous dopamine sources present in the auditory brainstem. This pathway represents a new mechanism to inhibit neurons by specifically regulating Ca(2+) channels directly involved in action potential initiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / physiology*
  • Calcium Channels, T-Type / physiology*
  • Cochlear Nucleus / physiology
  • Dopamine / physiology*
  • Electrochemistry
  • Electrophysiology
  • Immunohistochemistry
  • In Vitro Techniques
  • Interneurons / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred ICR
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Protein Kinase C / physiology
  • Receptors, Dopamine / physiology
  • Receptors, Dopamine D3 / physiology
  • Signal Transduction / physiology
  • Sodium Channels / physiology


  • Calcium Channels, T-Type
  • Potassium Channels
  • Receptors, Dopamine
  • Receptors, Dopamine D3
  • Sodium Channels
  • Protein Kinase C
  • Dopamine