{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"18204443"},"DateCompleted":{"Year":"2008","Month":"05","Day":"08"},"DateRevised":{"Year":"2025","Month":"05","Day":"29"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Print"},"@text":"1097-6256"},"JournalIssue":{"@attributes":{"CitedMedium":"Print"},"Volume":"11","Issue":"2","PubDate":{"Year":"2008","Month":"Feb"}},"Title":"Nature neuroscience","ISOAbbreviation":"Nat Neurosci"},"ArticleTitle":"Action potential generation requires a high sodium channel density in the axon initial segment.","Pagination":{"StartPage":"178","EndPage":"186","MedlinePgn":"178-86"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1038\/nn2040"}],"Abstract":{"AbstractText":["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."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Kole","ForeName":"Maarten H P","Initials":"MH","AffiliationInfo":[{"Affiliation":"Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ilschner","ForeName":"Susanne U","Initials":"SU"},{"@attributes":{"ValidYN":"Y"},"LastName":"Kampa","ForeName":"Bj\u00f6rn M","Initials":"BM"},{"@attributes":{"ValidYN":"Y"},"LastName":"Williams","ForeName":"Stephen R","Initials":"SR"},{"@attributes":{"ValidYN":"Y"},"LastName":"Ruben","ForeName":"Peter C","Initials":"PC"},{"@attributes":{"ValidYN":"Y"},"LastName":"Stuart","ForeName":"Greg J","Initials":"GJ"}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"MC_U105170644","Acronym":"MRC_","Agency":"Medical Research Council","Country":"United Kingdom"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2008","Month":"01","Day":"20"}]},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Nat Neurosci","NlmUniqueID":"9809671","ISSNLinking":"1097-6256"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D001572"},"@text":"Benzofurans"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D004988"},"@text":"Ethers, Cyclic"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D026941"},"@text":"Sodium Channel Blockers"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D015222"},"@text":"Sodium Channels"}},{"RegistryNumber":"124549-08-2","NameOfSubstance":{"@attributes":{"UI":"C061665"},"@text":"sodium-binding benzofuran isophthalate"}},{"RegistryNumber":"17466-45-4","NameOfSubstance":{"@attributes":{"UI":"D010590"},"@text":"Phalloidine"}},{"RegistryNumber":"3CHI920QS7","NameOfSubstance":{"@attributes":{"UI":"D003571"},"@text":"Cytochalasin B"}},{"RegistryNumber":"4368-28-9","NameOfSubstance":{"@attributes":{"UI":"D013779"},"@text":"Tetrodotoxin"}},{"RegistryNumber":"9NEZ333N27","NameOfSubstance":{"@attributes":{"UI":"D012964"},"@text":"Sodium"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D000200","MajorTopicYN":"N"},"@text":"Action Potentials"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"Y"},"@text":"physiology"},{"@attributes":{"UI":"Q000528","MajorTopicYN":"N"},"@text":"radiation effects"}]},{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D001369","MajorTopicYN":"N"},"@text":"Axons"},"QualifierName":[{"@attributes":{"UI":"Q000187","MajorTopicYN":"N"},"@text":"drug effects"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"Y"},"@text":"metabolism"},{"@attributes":{"UI":"Q000528","MajorTopicYN":"N"},"@text":"radiation effects"}]},{"DescriptorName":{"@attributes":{"UI":"D001572","MajorTopicYN":"N"},"@text":"Benzofurans"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D003198","MajorTopicYN":"N"},"@text":"Computer Simulation"}},{"DescriptorName":{"@attributes":{"UI":"D003571","MajorTopicYN":"N"},"@text":"Cytochalasin B"},"QualifierName":[{"@attributes":{"UI":"Q000494","MajorTopicYN":"N"},"@text":"pharmacology"}]},{"DescriptorName":{"@attributes":{"UI":"D004347","MajorTopicYN":"N"},"@text":"Drug 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Neurological"}},{"DescriptorName":{"@attributes":{"UI":"D009474","MajorTopicYN":"N"},"@text":"Neurons"},"QualifierName":[{"@attributes":{"UI":"Q000166","MajorTopicYN":"Y"},"@text":"cytology"},{"@attributes":{"UI":"Q000187","MajorTopicYN":"N"},"@text":"drug effects"},{"@attributes":{"UI":"Q000528","MajorTopicYN":"N"},"@text":"radiation effects"}]},{"DescriptorName":{"@attributes":{"UI":"D018408","MajorTopicYN":"N"},"@text":"Patch-Clamp Techniques"},"QualifierName":[{"@attributes":{"UI":"Q000379","MajorTopicYN":"N"},"@text":"methods"}]},{"DescriptorName":{"@attributes":{"UI":"D010590","MajorTopicYN":"N"},"@text":"Phalloidine"},"QualifierName":[{"@attributes":{"UI":"Q000494","MajorTopicYN":"N"},"@text":"pharmacology"}]},{"DescriptorName":{"@attributes":{"UI":"D051381","MajorTopicYN":"N"},"@text":"Rats"}},{"DescriptorName":{"@attributes":{"UI":"D017208","MajorTopicYN":"N"},"@text":"Rats, Wistar"}},{"DescriptorName":{"@attributes":{"UI":"D012964","MajorTopicYN":"N"},"@text":"Sodium"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D026941","MajorTopicYN":"N"},"@text":"Sodium Channel Blockers"},"QualifierName":[{"@attributes":{"UI":"Q000494","MajorTopicYN":"N"},"@text":"pharmacology"}]},{"DescriptorName":{"@attributes":{"UI":"D015222","MajorTopicYN":"N"},"@text":"Sodium Channels"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"Y"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D013003","MajorTopicYN":"N"},"@text":"Somatosensory Cortex"},"QualifierName":[{"@attributes":{"UI":"Q000166","MajorTopicYN":"N"},"@text":"cytology"},{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D013779","MajorTopicYN":"N"},"@text":"Tetrodotoxin"},"QualifierName":[{"@attributes":{"UI":"Q000494","MajorTopicYN":"N"},"@text":"pharmacology"}]}]}},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2007","Month":"10","Day":"15"},{"@attributes":{"PubStatus":"accepted"},"Year":"2007","Month":"12","Day":"17"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2008","Month":"1","Day":"22","Hour":"9","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2008","Month":"5","Day":"9","Hour":"9","Minute":"0"},{"@attributes":{"PubStatus":"entrez"},"Year":"2008","Month":"1","Day":"22","Hour":"9","Minute":"0"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"18204443"},{"@attributes":{"IdType":"doi"},"@text":"10.1038\/nn2040"},{"@attributes":{"IdType":"pii"},"@text":"nn2040"}]}}}}