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

Kole, Maarten; Ilschner, Susanne DR; Kampa, Bjoern; Williams, Stephen; Ruben, Peter; Stuart, Gregory J

Description

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...[Show more]

dc.contributor.authorKole, Maarten
dc.contributor.authorIlschner, Susanne DR
dc.contributor.authorKampa, Bjoern
dc.contributor.authorWilliams, Stephen
dc.contributor.authorRuben, Peter
dc.contributor.authorStuart, Gregory J
dc.date.accessioned2015-12-07T22:21:16Z
dc.identifier.issn1097-6256
dc.identifier.urihttp://hdl.handle.net/1885/19967
dc.description.abstractThe 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 μm-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.
dc.publisherNature Publishing Group
dc.sourceNature Neuroscience
dc.subjectKeywords: actin; sodium ion; voltage gated sodium channel; action potential; animal cell; animal experiment; article; controlled study; cytoskeleton; dendrite; density; imaging system; immunohistochemistry; nerve fiber; nonhuman; priority journal; pyramidal nerve c
dc.titleAction potential generation requires a high sodium channel density in the axon initial segment
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume11
dc.date.issued2008
local.identifier.absfor110901 - Autonomic Nervous System
local.identifier.ariespublicationu4693331xPUB10
local.type.statusPublished Version
local.contributor.affiliationKole, Maarten, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationIlschner, Susanne DR, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKampa, Bjoern, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWilliams, Stephen, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRuben, Peter, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationStuart, Gregory J, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage178
local.bibliographicCitation.lastpage186
local.identifier.doi10.1038/nn2040
dc.date.updated2015-12-07T08:55:52Z
local.identifier.scopusID2-s2.0-38649083179
local.identifier.thomsonID000252712100012
CollectionsANU Research Publications

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