Action potential generation requires a high sodium channel density in the axon initial segment

Nat Neurosci. 2008 Feb;11(2):178-86. doi: 10.1038/nn2040. Epub 2008 Jan 20.


The axon initial segment (AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium (Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel density at the AIS is similar to that at the soma and proximal dendrites. Here we provide data obtained by antibody staining, whole-cell voltage-clamp and Na(+) imaging, together with modeling, which indicate that the Na(+) channel density at the AIS of cortical pyramidal neurons is approximately 50 times that in the proximal dendrites. Anchoring of Na(+) channels to the cytoskeleton can explain this discrepancy, as disruption of the actin cytoskeleton increased the Na(+) current measured in patches from the AIS. Computational models required a high Na(+) channel density (approximately 2,500 pS microm(-2)) at the AIS to account for observations on action potential generation and backpropagation. In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Action Potentials / radiation effects
  • Animals
  • Axons / drug effects
  • Axons / metabolism*
  • Axons / radiation effects
  • Benzofurans / metabolism
  • Computer Simulation
  • Cytochalasin B / pharmacology
  • Drug Interactions
  • Electric Stimulation / methods
  • Ethers, Cyclic / metabolism
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Models, Neurological
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Phalloidine / pharmacology
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / metabolism*
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / physiology
  • Tetrodotoxin / pharmacology


  • Benzofurans
  • Ethers, Cyclic
  • Sodium Channel Blockers
  • Sodium Channels
  • sodium-binding benzofuran isophthalate
  • Phalloidine
  • Cytochalasin B
  • Tetrodotoxin
  • Sodium