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Articles, Cellular/Molecular

Fast-Onset Long-Term Open-State Block of Sodium Channels by A-type FHFs Mediates Classical Spike Accommodation in Hippocampal Pyramidal Neurons

Kumar Venkatesan, Yue Liu and Mitchell Goldfarb
Journal of Neuroscience 26 November 2014, 34 (48) 16126-16139; DOI: https://doi.org/10.1523/JNEUROSCI.1271-14.2014
Kumar Venkatesan
1Department of Biological Sciences, Hunter College of City University, New York, New York 10065 and
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Yue Liu
1Department of Biological Sciences, Hunter College of City University, New York, New York 10065 and
2The Graduate Center Neuroscience Training Subprogram at City University, New York, New York 10016
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Mitchell Goldfarb
1Department of Biological Sciences, Hunter College of City University, New York, New York 10065 and
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Abstract

Classical accommodation is a form of spike frequency adaptation in neurons whereby excitatory drive results in action potential output of gradually decreasing frequency. Here we describe an essential molecular component underlying classical accommodation in juvenile mouse hippocampal CA1 pyramidal neurons. A-type isoforms of fibroblast growth factor homologous factors (FHFs) bound to axosomatic voltage-gated sodium channels bear an N-terminal blocking particle that drives some associated channels into a fast-onset, long-term inactivated state. Use-dependent accumulating channel blockade progressively elevates spike voltage threshold and lengthens interspike intervals. The FHF particle only blocks sodium channels from the open state, and mutagenesis studies demonstrate that this particle uses multiple aliphatic and cationic residues to both induce and maintain the long-term inactivated state. The broad expression of A-type FHFs in neurons throughout the vertebrate CNS suggests a widespread role of these sodium channel modulators in the control of neural firing.

  • A-type FHF
  • accommodation
  • hippocampus
  • long-term inactivation
  • open-state block
  • voltage gated sodium channel
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The Journal of Neuroscience: 34 (48)
Journal of Neuroscience
Vol. 34, Issue 48
26 Nov 2014
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Fast-Onset Long-Term Open-State Block of Sodium Channels by A-type FHFs Mediates Classical Spike Accommodation in Hippocampal Pyramidal Neurons
Kumar Venkatesan, Yue Liu, Mitchell Goldfarb
Journal of Neuroscience 26 November 2014, 34 (48) 16126-16139; DOI: 10.1523/JNEUROSCI.1271-14.2014

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Fast-Onset Long-Term Open-State Block of Sodium Channels by A-type FHFs Mediates Classical Spike Accommodation in Hippocampal Pyramidal Neurons
Kumar Venkatesan, Yue Liu, Mitchell Goldfarb
Journal of Neuroscience 26 November 2014, 34 (48) 16126-16139; DOI: 10.1523/JNEUROSCI.1271-14.2014
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Keywords

  • A-type FHF
  • accommodation
  • hippocampus
  • long-term inactivation
  • open-state block
  • voltage gated sodium channel

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