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

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

Author information

1
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia.

Abstract

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.

PMID:
18204443
DOI:
10.1038/nn2040
[Indexed for MEDLINE]

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