Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation
- PMID: 19633666
- DOI: 10.1038/nn.2359
Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation
Abstract
The distal end of the axon initial segment (AIS) is the preferred site for action potential initiation in cortical pyramidal neurons because of its high Na(+) channel density. However, it is not clear why action potentials are not initiated at the proximal AIS, which has a similarly high Na(+) channel density. We found that low-threshold Na(v)1.6 and high-threshold Na(v)1.2 channels preferentially accumulate at the distal and proximal AIS, respectively, and have distinct functions in action potential initiation and backpropagation. Patch-clamp recording from the axon cut end of pyramidal neurons in the rat prefrontal cortex revealed a high density of Na(+) current and a progressive reduction in the half-activation voltage (up to 14 mV) with increasing distance from the soma at the AIS. Further modeling studies and simultaneous somatic and axonal recordings showed that distal Na(v)1.6 promotes action potential initiation, whereas proximal Na(v)1.2 promotes its backpropagation to the soma.
Comment in
-
Who let the spikes out?Nat Neurosci. 2009 Aug;12(8):959-60. doi: 10.1038/nn0809-959. Nat Neurosci. 2009. PMID: 19636347 Free PMC article. No abstract available.
Similar articles
-
Neuronal signaling in central nervous system.Sheng Li Xue Bao. 2011 Feb 25;63(1):1-8. Sheng Li Xue Bao. 2011. PMID: 21340428 Review.
-
Role of sodium channel subtype in action potential generation by neocortical pyramidal neurons.Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7184-E7192. doi: 10.1073/pnas.1720493115. Epub 2018 Jul 10. Proc Natl Acad Sci U S A. 2018. PMID: 29991598 Free PMC article.
-
Action potential generation requires a high sodium channel density in the axon initial segment.Nat Neurosci. 2008 Feb;11(2):178-86. doi: 10.1038/nn2040. Epub 2008 Jan 20. Nat Neurosci. 2008. PMID: 18204443
-
Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons.J Neurophysiol. 2008 Oct;100(4):2361-80. doi: 10.1152/jn.90332.2008. Epub 2008 Jul 23. J Neurophysiol. 2008. PMID: 18650312
-
Axonal bleb recording.Neurosci Bull. 2012 Aug;28(4):342-50. doi: 10.1007/s12264-012-1247-1. Neurosci Bull. 2012. PMID: 22833034 Free PMC article. Review.
Cited by
-
Recurrent and Non-Recurrent Mutations of SCN8A in Epileptic Encephalopathy.Front Neurol. 2015 May 15;6:104. doi: 10.3389/fneur.2015.00104. eCollection 2015. Front Neurol. 2015. PMID: 26029160 Free PMC article. Review.
-
Reemerging role of cable properties in action potential initiation.Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3715-6. doi: 10.1073/pnas.1300520110. Epub 2013 Feb 25. Proc Natl Acad Sci U S A. 2013. PMID: 23440200 Free PMC article. No abstract available.
-
The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin.Epilepsia. 2016 Sep;57(9):1458-66. doi: 10.1111/epi.13461. Epub 2016 Jul 4. Epilepsia. 2016. PMID: 27375106 Free PMC article.
-
Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons.PLoS One. 2015 Jun 17;10(6):e0130250. doi: 10.1371/journal.pone.0130250. eCollection 2015. PLoS One. 2015. PMID: 26083350 Free PMC article.
-
It Takes Two to Tango: Channel Interplay Leads to Paradoxical Hyperexcitability in a Loss-of-Function Epilepsy Variant.Epilepsy Curr. 2021 Nov 24;22(1):69-71. doi: 10.1177/15357597211057966. eCollection 2022 Jan-Feb. Epilepsy Curr. 2021. PMID: 35233206 Free PMC article. No abstract available.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases