A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents.

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  • Additional Information
    • Source:
      Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : Society for Neuroscience
      Original Publication: [Baltimore, Md.] : The Society, c1981-
    • Subject Terms:
      Action Potentials*/physiology ; Purkinje Cells*/physiology ; Sodium Channels*/physiology ; Sodium Channels*/metabolism; Animals ; Mice ; Female ; Male ; Sodium/metabolism ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Models, Neurological
    • Abstract:
      The resurgent sodium current (I NaR ) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I NaR is thought to drive high rates of repetitive neuronal firing. However, I NaR is often studied in combination with the persistent or noninactivating portion of sodium currents (I NaP ). We used dynamic clamp to test how I NaR and I NaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned I NaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold I NaP is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed I NaP and I NaR can be inversely scaled by adjusting occupancy in the slow-inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune I NaP and Purkinje neuron repetitive firing rates.
      Competing Interests: The authors declare no competing financial interests.
      (Copyright © 2024 the authors.)
    • Comments:
      Update of: bioRxiv. 2024 Jun 01:2023.10.25.564042. doi: 10.1101/2023.10.25.564042. (PMID: 38187680)
    • References:
      Exp Brain Res. 1967;4(1):43-57. (PMID: 4386325)
      J Neurosci. 1999 Mar 1;19(5):1663-74. (PMID: 10024353)
      J Neurophysiol. 2013 Sep;110(5):1144-57. (PMID: 23741036)
      Elife. 2022 Jan 25;11:. (PMID: 35076394)
      Neuron. 1994 Sep;13(3):703-12. (PMID: 7917300)
      J Neurosci. 2006 Feb 15;26(7):1935-44. (PMID: 16481425)
      Neuron. 2012 Sep 20;75(6):1081-93. (PMID: 22998875)
      Neuron. 1997 Oct;19(4):881-91. (PMID: 9354334)
      J Neurophysiol. 1968 Sep;31(5):785-97. (PMID: 4974877)
      Neuron. 2006 Feb 2;49(3):409-20. (PMID: 16446144)
      Biophys J. 2001 Feb;80(2):729-37. (PMID: 11159440)
      J Neurosci. 2003 Jun 15;23(12):4899-912. (PMID: 12832512)
      Biophys J. 2007 Mar 15;92(6):1938-51. (PMID: 17189307)
      Handb Exp Pharmacol. 2014;221:33-49. (PMID: 24737231)
      PLoS One. 2016 Mar 10;11(3):e0150761. (PMID: 26963710)
      Nat Rev Neurosci. 2013 Jan;14(1):49-62. (PMID: 23232607)
      J Neurophysiol. 2015 May 1;113(9):3172-85. (PMID: 25787950)
      Nat Commun. 2021 Nov 19;12(1):6762. (PMID: 34799550)
      J Neurosci. 2002 Dec 15;22(24):10603-12. (PMID: 12486152)
      J Physiol. 2023 Dec;601(23):5147-5164. (PMID: 37837315)
      Front Cell Neurosci. 2007 Dec 30;1:2. (PMID: 18946520)
      Neuron. 2002 Feb 14;33(4):587-600. (PMID: 11856532)
      J Gen Physiol. 2018 Nov 5;150(11):1523-1540. (PMID: 30301870)
      Exp Brain Res. 1970 Nov 26;11(4):327-42. (PMID: 5496934)
      J Physiol. 2020 Jan;598(2):381-401. (PMID: 31715021)
      J Neurophysiol. 1968 Mar;31(2):131-41. (PMID: 5687379)
      J Gen Physiol. 1997 Jul;110(1):23-33. (PMID: 9234168)
      J Neurosci. 2010 Apr 21;30(16):5629-34. (PMID: 20410115)
      Cell Rep. 2017 Apr 18;19(3):532-544. (PMID: 28423317)
      J Neurophysiol. 2001 Jan;85(1):472-5. (PMID: 11152749)
      Front Cell Neurosci. 2021 Oct 01;15:760610. (PMID: 34658797)
      J Physiol. 2014 Nov 15;592(22):4825-38. (PMID: 25172941)
      J Physiol. 1980 Aug;305:171-95. (PMID: 7441552)
      J Neurophysiol. 2004 Nov;92(5):2831-43. (PMID: 15212420)
      J Neurosci. 1997 Jun 15;17(12):4517-26. (PMID: 9169512)
      J Neurosci. 2004 Apr 7;24(14):3511-21. (PMID: 15071098)
      Experientia. 1964 Oct 15;20(10):575-6. (PMID: 5859224)
      Nat Commun. 2014 Nov 21;5:5525. (PMID: 25413837)
      J Gen Physiol. 2019 Nov 4;151(11):1300-1318. (PMID: 31558566)
      J Clin Invest. 2010 Jan;120(1):369-78. (PMID: 20038812)
      J Biol Chem. 2014 Jan 24;289(4):1971-80. (PMID: 24311784)
      J Neurosci. 2008 Oct 22;28(43):11079-88. (PMID: 18945915)
      Neuron. 2003 Jul 3;39(1):109-20. (PMID: 12848936)
      J Physiol. 1966 Jan;182(2):268-96. (PMID: 5944665)
      Cell Mol Life Sci. 2018 Oct;75(19):3495-3505. (PMID: 29982847)
      Neuron. 1997 Sep;19(3):665-78. (PMID: 9331356)
    • Grant Information:
      R15 NS125560 United States NS NINDS NIH HHS
    • Contributed Indexing:
      Keywords: dynamic clamp; intrinsic excitability; membrane excitability; persistent sodium; resurgent sodium; sodium channel
    • Accession Number:
      0 (Sodium Channels)
      9NEZ333N27 (Sodium)
    • Publication Date:
      Date Created: 20240610 Date Completed: 20240717 Latest Revision: 20240720
    • Publication Date:
      20240720
    • Accession Number:
      PMC11255426
    • Accession Number:
      10.1523/JNEUROSCI.2396-23.2024
    • Accession Number:
      38858080