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Long‐term inactivation particle for voltage‐gated sodium channels
Author(s) -
Dover Katarzyna,
Solinas Sergio,
D’Angelo Egidio,
Goldfarb Mitchell
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.192559
Subject(s) - depolarization , sodium channel , biophysics , chemistry , membrane potential , repolarization , voltage gated ion channel , protein subunit , ion channel , electrophysiology , microbiology and biotechnology , biochemistry , sodium , biology , neuroscience , receptor , organic chemistry , gene
Action potential generation is governed by the opening, inactivation, and recovery of voltage‐gated sodium channels. A channel's voltage‐sensing and pore‐forming α subunit bears an intrinsic fast inactivation particle that mediates both onset of inactivation upon membrane depolarization and rapid recovery upon repolarization. We describe here a novel inactivation particle housed within an accessory channel subunit (A‐type FHF protein) that mediates rapid‐onset, long‐term inactivation of several sodium channels. The channel‐intrinsic and tethered FHF‐derived particles, both situated at the cytoplasmic face of the plasma membrane, compete for induction of inactivation, causing channels to progressively accumulate into the long‐term refractory state during multiple cycles of membrane depolarization. Intracellular injection of a short peptide corresponding to the FHF particle can reproduce channel long‐term inactivation in a dose‐dependent manner and can inhibit repetitive firing of cerebellar granule neurons. We discuss potential structural mechanisms of long‐term inactivation and potential roles of A‐type FHFs in the modulation of action potential generation and conduction.