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

Venkatesan, K. and Liu, Y. and Goldfarb, M. (2014) Fast-Onset Long-Term Open-State Block of Sodium Channels by A-type FHFs Mediates Classical Spike Accommodation in Hippocampal Pyramidal Neurons. Journal of Neuroscience, 34 (48). pp. 16126-16139. ISSN 0270-6474

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Official URL: http://dx.doi.org/10.1523/JNEUROSCI.1271-14.2014

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 voltagethreshold 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.

Item Type: Article
Subjects: Pharmaceutical Sciences
Pharmacy
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Dr KUMAR Venkatesan
Date Deposited: 14 Jun 2017 10:53
Last Modified: 14 Jun 2017 10:53
URI: http://eprints.kku.edu.sa/id/eprint/769

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