CoChat
Sign Up
Cited by 86Ion channel regulation and functionNeuroscience and Neuropharmacology Researchstochastic dynamics and bifurcation

Transient sodium current at subthreshold voltages: activation by EPSP waveforms

Open access
Carter, Brett C., Giessel, Andrew J., Sabatini, Bernardo L., Bean, Bruce P.·2012·Neuron
DOI 10.1016/j.neuron.2012.08.033PMC PMC3460524
Open this paper in CoChat — free accountOpen PDF

Abstract

Tetrodotoxin (TTX)-sensitive sodium channels carry large transient currents during action potentials and also "persistent" sodium current, a noninactivating TTX-sensitive current present at subthreshold voltages. We examined gating of subthreshold sodium current in dissociated cerebellar Purkinje neurons and hippocampal CA1 neurons, studied at 37°C with near-physiological ionic conditions. Unexpectedly, in both cell types small voltage steps at subthreshold voltages activated a substantial component of transient sodium current as well as persistent current. Subthreshold EPSP-like waveforms also activated a large component of transient sodium current, but IPSP-like waveforms engaged primarily persistent sodium current with only a small additional transient component. Activation of transient as well as persistent sodium current at subthreshold voltages produces amplification of EPSPs that is sensitive to the rate of depolarization and can help account for the dependence of spike threshold on depolarization rate, as previously observed in vivo.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuron.2012.08.033

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Voltage signals from the dendrite propagate without attenuation into spines, but synaptic potentials generated inside the spine head are filtered when they travel to the dendrite.

    “This means that voltage signals from the dendrite propagate without attenuation into the spines (Holthoff et al., 2010; Carter et al., 2012; Popovic et al., 2014), but synaptic potentials generated inside the spine head are filtered when they travel to the dendrite (Araya et al., 2006, 2014; Harnett et al., 2012).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Carter et al., 2012

    Carter et al. is cited for the first clause, about dendrite-to-spine voltage propagation; the second clause has separate citations. The Results section on single-spine glutamate uncaging reports EPSP amplification, but no passage found in our copy addresses whether dendritic voltage signals enter spines without attenuation (searched for dendrite-to-spine propagation and spine-neck attenuation). (LLM, conf=0.75)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 86 · Cited by 86

Research works printed but not linked: 78

  1. Agrawal N Alonso A Ragsdale DS Increased persistent sodium currents in rat entorhinal cortex layer V neurons in a post-status epilepticus model of temporal lobe epilepsy Epilepsia 2003 44 1601 1604 14636336
  2. Alzheimer C Schwindt PC Crill WE Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex J Neurosci 1993 13 660 673 8381170 PMC6576639
  3. Aman TK Raman IM Subunit dependence of Na channel slow inactivation and open channel block in cerebellar neurons Biophys J 2007 92 1938 1951 17189307 PMC1861793
  4. Aman TK Raman IM Inwardly permeating Na ions generate the voltage dependence of resurgent Na current in cerebellar Purkinje neurons J Neurosci 2010 30 5629 5634 20410115 PMC2865843
  5. Andreasen M Lambert JD Somatic amplification of distally generated subthreshold EPSPs in rat hippocampal pyramidal neurones J Physiol 1999 519 Pt 1 85 100 10432341 PMC2269499
  6. Araya R Nikolenko V Eisenthal KB Yuste R Sodium channels amplify spine potentials Proc Natl Acad Sci U S A 2007 104 12347 12352 17640908 PMC1924793
  7. Artinian J Peret A Marti G Epsztein J Crepel V Synaptic kainate receptors in interplay with INaP shift the sparse firing of dentate granule cells to a sustained rhythmic mode in temporal lobe epilepsy J Neurosci 31 10811 10818 21795533 PMC6623106
  8. Axmacher N Miles R Intrinsic cellular currents and the temporal precision of EPSP-action potential coupling in CA1 pyramidal cells J Physiol 2004 555 713 725 14724200 PMC1664854
  9. Azouz R Gray CM Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo Proc Natl Acad Sci U S A 2000 97 8110 8115 10859358 PMC16678
  10. Azouz R Jensen MS Yaari Y Ionic basis of spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells J Physiol 1996 492 Pt 1 211 223 8730596 PMC1158874
  11. Bevan MD Wilson CJ Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons J Neurosci 1999 19 7617 7628 10460267 PMC6782508
  12. Cardin JA Kumbhani RD Contreras D Palmer LA Cellular mechanisms of temporal sensitivity in visual cortex neurons J Neurosci 2010 30 3652 3662 20219999 PMC2880457
  13. Carter AG Sabatini BL State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons Neuron 2004 44 483 493 15504328
  14. Carter BC Bean BP Sodium entry during action potentials of mammalian neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons Neuron 2009 64 898 909 20064395 PMC2810867
  15. Carter BC Bean BP Incomplete inactivation and rapid recovery of voltage-dependent sodium channels during high-frequency firing in cerebellar Purkinje neurons J Neurophysiol 2011 105 860 871 21160003 PMC3059179
  16. Castelli L Nigro MJ Magistretti J Analysis of resurgent sodium-current expression in rat parahippocampal cortices and hippocampal formation Brain Res 2007 1163 44 55 17628510
  17. Catterall WA From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels Neuron 2000 26 13 25 10798388
  18. Chen S Su H Yue C Remy S Royeck M Sochivko D Opitz T Beck H Yaari Y An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus J Neurophysiol 2011 105 117 129 20980543
  19. Crill WE Persistent sodium current in mammalian central neurons Annu Rev Physiol 1996 58 349 362 8815799
  20. D’Angelo E De Filippi G Rossi P Taglietti V Ionic mechanism of electroresponsiveness in cerebellar granule cells implicates the action of a persistent sodium current J Neurophysiol 1998 80 493 503 9705445
  21. de Polavieja GG Harsch A Kleppe I Robinson HP Juusola M Stimulus history reliably shapes action potential waveforms of cortical neurons J Neurosci 2005 25 5657 5665 15944394 PMC6724966
  22. Deisz RA Fortin G Zieglgansberger W Voltage dependence of excitatory postsynaptic potentials of rat neocortical neurons J Neurophysiol 1991 65 371 382 1826741
  23. Del Negro CA Koshiya N Butera RJ Jr. Smith JC Persistent sodium current, membrane properties and bursting behavior of pre-botzinger complex inspiratory neurons in vitro J Neurophysiol 2002 88 2242 2250 12424266
  24. Destexhe A Paré D Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo J Neurophysiol 1999 81 1531 1547 10200189
  25. Destexhe A Rudolph M Paré D The high-conductance state of neocortical neurons in vivo Nat Rev Neurosci 2003 4 739 751 12951566
  26. Do MT Bean BP Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation Neuron 2003 39 109 120 12848936
  27. Enomoto A Han JM Hsiao CF Chandler SH Sodium currents in mesencephalic trigeminal neurons from Nav1.6 null mice J Neurophysiol 2007 98 710 719 17522178
  28. Fleidervish IA Gutnick MJ Kinetics of slow inactivation of persistent sodium current in layer V neurons of mouse neocortical slices J Neurophysiol 1996 76 2125 2130 8890326
  29. French CR Sah P Buckett KJ Gage PW A voltage-dependent persistent sodium current in mammalian hippocampal neurons J Gen Physiol 1990 95 1139 1157 2374000 PMC2216358
  30. Fricker D Miles R EPSP amplification and the precision of spike timing in hippocampal neurons Neuron 2000 28 559 569 11144364
  31. Giessel AJ Sabatini BL M1 muscarinic receptors boost synaptic potentials and calcium influx in dendritic spines by inhibiting postsynaptic SK channels Neuron 2010 68 936 947 21145006 PMC3052967
  32. Gittis AH Moghadam SH du Lac S Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents J Neurophysiol 104 1625 1634 20592126 PMC2944688
  33. Gonzalez-Burgos G Barrionuevo G Voltage-gated sodium channels shape subthreshold EPSPs in layer 5 pyramidal neurons from rat prefrontal cortex J Neurophysiol 2001 86 1671 1684 11600631
  34. Gutfreund Y yarom Y Segev I Subthreshold oscillations and resonant frequency in guinea-pig cortical neurons: physiology and modelling J Physiol 1995 483 Pt 3 621 640 7776248 PMC1157807
  35. Haider B Duque A Hasenstaub AR McCormick DA Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition J Neurosci 2006 26 4535 4545 16641233 PMC6674060
  36. Hardie JB Pearce RA Active and passive membrane properties and intrinsic kinetics shape synaptic inhibition in hippocampal CA1 pyramidal neurons J Neurosci 2006 26 8559 8569 16914682 PMC6674351
  37. Hotson JR Prince DA Schwartzkroin PA Anomalous inward rectification in hippocampal neurons J Neurophysiol 1979 42 889 895 430121
  38. Hu H Vervaeke K Graham LJ Storm JF Complementary theta resonance filtering by two spatially segregated mechanisms in CA1 hippocampal pyramidal neurons J Neurosci 2009 29 14472 14483 19923281 PMC6665813
  39. Hu H Vervaeke K Storm JF Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells J Physiol 2002 545 783 805 12482886 PMC2290731
  40. Hu H Vervaeke K Storm JF M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region J Neurosci 2007 27 1853 1867 17314282 PMC6673553
  41. Huang H Trussell LO Control of presynaptic function by a persistent Na(+) current Neuron 2008 60 975 979 19109905 PMC2657474
  42. Isope P Barbour B Properties of unitary granule cell-->Purkinje cell synapses in adult rat cerebellar slices J Neurosci 2002 22 9668 9678 12427822 PMC6757845
  43. Kay AR Sugimori M Llinas R Kinetic and stochastic properties of a persistent sodium current in mature guinea pig cerebellar Purkinje cells J Neurophysiol 1998 80 1167 1179 9744930
  44. Kodama T Guerrero S Shin M Moghadam S Faulstich M du Lac S Neuronal Classification and Marker Gene Identification via Single-Cell Expression Profiling of Brainstem Vestibular Neurons Subserving Cerebellar Learning J Neurosci 32 7819 7831 22674258 PMC3410725
  45. Kuo CC Bean BP Na+ channels must deactivate to recover from inactivation Neuron 1994 12 819 829 8161454
  46. Kuo JJ Lee RH Zhang L Heckman CJ Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones J Physiol 2006 574 819 834 16728453 PMC1817738
  47. Leão RM Kushmerick C Pinaud R Renden R Li GL Taschenberger H Spirou G Levinson SR von Gersdorff H Presynaptic Na+ channels: locus, development, and recovery from inactivation at a high-fidelity synapse J Neurosci 2005 25 3724 3738 15814803 PMC4511161
  48. Lipowsky R Gillessen T Alzheimer C Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells J Neurophysiol 1996 76 2181 2191 8899593
  49. Lorincz A Nusser Z Cell-type-dependent molecular composition of the axon initial segment J Neurosci 2008 28 14329 14340 19118165 PMC2628579
  50. Magistretti J Alonso A Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and single-channel study J Gen Physiol 1999 114 491 509 10498669 PMC2229464
  51. Magistretti J Alonso A Fine gating properties of channels responsible for persistent sodium current generation in entorhinal cortex neurons J Gen Physiol 2002 120 855 873 12451054 PMC2229567
  52. Magistretti J Ragsdale DS Alonso A High conductance sustained single-channel activity responsible for the low-threshold persistent Na(+) current in entorhinal cortex neurons J Neurosci 1999 19 7334 7341 10460240 PMC6782527
  53. Mainen ZF Sejnowski TJ Reliability of spike timing in neocortical neurons Science 1995 268 1503 1506 7770778
  54. Maurice N Tkatch T Meisler M Sprunger LK Surmeier DJ D1/D5 dopamine receptor activation differentially modulates rapidly inactivating and persistent sodium currents in prefrontal cortex pyramidal neurons J Neurosci 2001 21 2268 2277 11264302 PMC6762404
  55. Menon V Spruston N Kath WL A state-mutating genetic algorithm to design ion-channel models Proc Natl Acad Sci U S A 2009 106 16829 16834 19805381 PMC2757850
  56. Mickus T Jung H Spruston N Properties of slow, cumulative sodium channel inactivation in rat hippocampal CA1 pyramidal neurons Biophys J 1999 76 846 860 9929486 PMC1300086
  57. Milescu LS Yamanishi T Ptak K Smith JC Kinetic properties and functional dynamics of sodium channels during repetitive spiking in a slow pacemaker neuron J Neurosci 2010 30 12113 12127 20826674 PMC2945634
  58. Mittmann W Hausser M Linking synaptic plasticity and spike output at excitatory and inhibitory synapses onto cerebellar Purkinje cells J Neurosci 2007 27 5559 5570 17522301 PMC6672768
  59. Neher E Correction for liquid junction potentials in patch clamp experiments Methods Enzymol 1992 207 123 131 1528115
  60. Nowak LG Sanchez-Vives MV McCormick DA Influence of low and high frequency inputs on spike timing in visual cortical neurons Cereb Cortex 1997 7 487 501 9276174
  61. Osorio N Cathala L Meisler MH Crest M Magistretti J Delmas P Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells J Physiol 2010 588 651 670 20173079 PMC2828138
  62. Ramakers GM Storm JF A postsynaptic transient K(+) current modulated by arachidonic acid regulates synaptic integration and threshold for LTP induction in hippocampal pyramidal cells Proc Natl Acad Sci U S A 2002 99 10144 10149 12114547 PMC126638
  63. Raman IM Bean BP Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms Biophys J 2001 80 729 737 11159440 PMC1301271
  64. Royeck M Horstmann MT Remy S Reitze M Yaari Y Beck H Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons J Neurophysiol 2008 100 2361 2380 18650312
  65. Schwindt PC Crill WE Amplification of synaptic current by persistent sodium conductance in apical dendrite of neocortical neurons J Neurophysiol 1995 74 2220 2224 8592214
  66. Shah MM Migliore M Brown DA Differential effects of Kv7 (M-) channels on synaptic integration in distinct subcellular compartments of rat hippocampal pyramidal neurons J Physiol 2011 589 6029 6038 22041186 PMC3245855
  67. Stafstrom CE Persistent sodium current and its role in epilepsy Epilepsy Curr 2007 7 15 22 17304346 PMC1797888
  68. Stuart G Voltage-activated sodium channels amplify inhibition in neocortical pyramidal neurons Nat Neurosci 1999 2 144 150 10195198
  69. Stuart G Sakmann B Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons Neuron 1995 15 1065 1076 7576650
  70. Taddese A Bean BP Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons Neuron 2002 33 587 600 11856532
  71. Vervaeke K Hu H Graham LJ Storm JF Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing Neuron 2006 49 257 270 16423699
  72. Vreugdenhil M Hoogland G van Veelen CW Wadman WJ Persistent sodium current in subicular neurons isolated from patients with temporal lobe epilepsy Eur J Neurosci 2004 19 2769 2778 15147310
  73. White JA Klink R Alonso A Kay AR Noise from voltage-gated ion channels may influence neuronal dynamics in the entorhinal cortex J Neurophysiol 1998 80 262 269 9658048
  74. Wickens JR Wilson CJ Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo J Neurophysiol 1998 79 2358 2364 9582211
  75. Wilent WB Contreras D Stimulus-dependent changes in spike threshold enhance feature selectivity in rat barrel cortex neurons J Neurosci 2005a 25 2983 2991 15772358 PMC6725135
  76. Williams SR Stuart GJ Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons J Physiol 1999 521 Pt 2 467 482 10581316 PMC2269673
  77. Wu N Enomoto A Tanaka S Hsiao CF Nykamp DQ Izhikevich E Chandler SH Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability J Neurophysiol 2005 93 2710 2722 15625100
  78. Yue C Remy S Su H Beck H Yaari Y Proximal persistent Na+ channels drive spike after depolarizations and associated bursting in adult CA1 pyramidal cells J Neurosci 2005 25 9704 9720 16237175 PMC6725731

Authors
Carter, B. C., Giessel, A. J., Sabatini, B. L., & Bean, B. P.
Affiliations
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Bean, Bruce P.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2012-09
Volume
75
Issue
6
Pages
1081-1093
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2012.08.033
PMC
PMC3460524
OpenAlex
W2051743763
Cited by
86
References
86
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 3 · 2012: 1
FWCI
2.83
Type
journal article
Language
en
Update notices
erratum (2015-08-19)
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Neurological Disorders and Stroke (R01NS036855, R01NS046579, F31NS065647, F31NS064630)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
Keywords
transient sodium current, persistent sodium current, excitatory postsynaptic potentials, inhibitory postsynaptic potentials, Purkinje cells, CA1 pyramidal neurons, depolarization rate, spike threshold, tetrodotoxin-sensitive sodium channels
MeSH terms
Animals, Animals, Newborn, Cerebellum, Electric Stimulation, Hippocampus, Markov Chains, Mice, Inbred C57BL, Models, Neurological, Neurons, Tetrodotoxin, Sodium Channels, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Sodium Channel Blockers, Mice, Biophysical Phenomena, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review