Jul 28, 2009

Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation

Nature Neuroscience
Wenqin HuYousheng Shu

Abstract

The distal end of the axon initial segment (AIS) is the preferred site for action potential initiation in cortical pyramidal neurons because of its high Na(+) channel density. However, it is not clear why action potentials are not initiated at the proximal AIS, which has a similarly high Na(+) channel density. We found that low-threshold Na(v)1.6 and high-threshold Na(v)1.2 channels preferentially accumulate at the distal and proximal AIS, respectively, and have distinct functions in action potential initiation and backpropagation. Patch-clamp recording from the axon cut end of pyramidal neurons in the rat prefrontal cortex revealed a high density of Na(+) current and a progressive reduction in the half-activation voltage (up to 14 mV) with increasing distance from the soma at the AIS. Further modeling studies and simultaneous somatic and axonal recordings showed that distal Na(v)1.6 promotes action potential initiation, whereas proximal Na(v)1.2 promotes its backpropagation to the soma.

  • References44
  • Citations253

Mentioned in this Paper

Initial Segment of Axon
Neurons
Action Potentials
Transcription Initiation
PDZK1 gene
Structure of Cortex of Kidney
Clamping Activity
Prefrontal Cortex (Walker)
Cerebral Cortex
SCN2A wt Allele

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