Action potential generation requires a high sodium channel density in the axon initial segment - PubMed (original) (raw)
doi: 10.1038/nn2040. Epub 2008 Jan 20.
Affiliations
- PMID: 18204443
- DOI: 10.1038/nn2040
Action potential generation requires a high sodium channel density in the axon initial segment
Maarten H P Kole et al. Nat Neurosci. 2008 Feb.
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.
Similar articles
- Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation.
Hu W, Tian C, Li T, Yang M, Hou H, Shu Y. Hu W, et al. Nat Neurosci. 2009 Aug;12(8):996-1002. doi: 10.1038/nn.2359. Epub 2009 Jul 26. Nat Neurosci. 2009. PMID: 19633666 - Functional distribution of three types of Na+ channel on soma and processes of dorsal horn neurones of rat spinal cord.
Safronov BV, Wolff M, Vogel W. Safronov BV, et al. J Physiol. 1997 Sep 1;503 ( Pt 2)(Pt 2):371-85. doi: 10.1111/j.1469-7793.1997.371bh.x. J Physiol. 1997. PMID: 9306279 Free PMC article. - Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons.
Medvedeva YV, Kim MS, Schnizler K, Usachev YM. Medvedeva YV, et al. Neuroscience. 2009 Mar 17;159(2):559-69. doi: 10.1016/j.neuroscience.2008.12.029. Epub 2008 Dec 30. Neuroscience. 2009. PMID: 19162133 - Neuronal signaling in central nervous system.
Shu Y. Shu Y. Sheng Li Xue Bao. 2011 Feb 25;63(1):1-8. Sheng Li Xue Bao. 2011. PMID: 21340428 Review. - Contribution of Axon Initial Segment Structure and Channels to Brain Pathology.
Garrido JJ. Garrido JJ. Cells. 2023 Apr 21;12(8):1210. doi: 10.3390/cells12081210. Cells. 2023. PMID: 37190119 Free PMC article. Review.
Cited by
- Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current.
Viteri JA, Bueschke N, Santin JM, Arnold WD. Viteri JA, et al. Geroscience. 2024 Oct 30. doi: 10.1007/s11357-024-01405-8. Online ahead of print. Geroscience. 2024. PMID: 39472350 - Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.
Zhao R, Ren B, Xiao Y, Tian J, Zou Y, Wei J, Qi Y, Hu A, Xie X, Huang ZJ, Shu Y, He M, Lu J, Tai Y. Zhao R, et al. Sci Adv. 2024 Aug 2;10(31):eadk4331. doi: 10.1126/sciadv.adk4331. Epub 2024 Aug 2. Sci Adv. 2024. PMID: 39093969 Free PMC article. - Multi-scale modelling of location- and frequency-dependent synaptic plasticity induced by transcranial magnetic stimulation in the dendrites of pyramidal neurons.
Hananeia N, Ebner C, Galanis C, Cuntz H, Opitz A, Vlachos A, Jedlicka P. Hananeia N, et al. bioRxiv [Preprint]. 2024 Jul 5:2024.07.03.601851. doi: 10.1101/2024.07.03.601851. bioRxiv. 2024. PMID: 39005474 Free PMC article. Preprint. - Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.
Thome C, Janssen JM, Karabulut S, Acuna C, D'Este E, Soyka SJ, Baum K, Bock M, Lehmann N, Roos J, Stevens NA, Hasegawa M, Ganea DA, Benoit CM, GrĂ¼ndemann J, Min L, Bird KM, Schultz C, Bennett V, Jenkins PM, Engelhardt M. Thome C, et al. bioRxiv [Preprint]. 2024 Jun 19:2023.02.01.525891. doi: 10.1101/2023.02.01.525891. bioRxiv. 2024. PMID: 38948770 Free PMC article. Preprint. - Optimization of an anatomically and electrically detailed rodent subthalamic nucleus neuron model.
Chen H, Noor MS, Bingham CS, McIntyre CC. Chen H, et al. J Neurophysiol. 2024 Jul 1;132(1):136-146. doi: 10.1152/jn.00287.2023. Epub 2024 Jun 12. J Neurophysiol. 2024. PMID: 38863430 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous