Article abstract
Nature Neuroscience 11, 178 - 186 (2008)
Published online: 20 January 2008 | doi:10.1038/nn2040
Action potential generation requires a high sodium channel density in the axon initial segment
Maarten H P Kole1, Susanne U Ilschner1, Björn M Kampa1,4, Stephen R Williams1,2, Peter C Ruben1,3 & Greg J Stuart1
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 
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 (2,500 pS 
m-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.
- Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia.
- Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
- School of Kinesiology, Simon Fraser University, 8888 University Drive, Vancouver, British Columbia V5A 1S6, Canada.
- Present address: Brain Research Institute, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Correspondence to: Greg J Stuart1 e-mail: greg.stuart@anu.edu.au
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