title: Action potential generation requires a high sodium channel density in the axon initial segment.
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.
authors.affiliation: Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia.
authors.forename: Maarten H P
authors.initials: MH
authors.lastname: Kole
authors.forename: Susanne U
authors.initials: SU
authors.lastname: Ilschner
authors.forename: Björn M
authors.initials: BM
authors.lastname: Kampa
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Williams
authors.forename: Peter C
authors.initials: PC
authors.lastname: Ruben
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stuart
mesh_terms: D000200:Action Potentials / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D001572:Benzofurans / Q000378:metabolism; D003198:Computer Simulation; D003571:Cytochalasin B / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004988:Ethers, Cyclic / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010590:Phalloidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D001572:Benzofurans; D004988:Ethers, Cyclic; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C061665:sodium-binding benzofuran isophthalate; D010590:Phalloidine; D003571:Cytochalasin B; D013779:Tetrodotoxin; D012964:Sodium