title: Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation.
abstract: Most action potentials are produced by the sequential activation of voltage-gated sodium (Nav) and potassium (Kv) channels. This is mainly achieved by the rapid conformational rearrangement of voltage-sensor (VS) modules in Nav channels, with activation kinetics up to 6-fold faster than Shaker-type Kv channels. Here, using mutagenesis and gating current measurements, we show that a 3-fold acceleration of the VS kinetics in Nav versus Shaker Kv channels is produced by the hydrophilicity of two "speed-control" residues located in the S2 and S4 segments in Nav domains I-III. An additional 2-fold acceleration of the Nav VS kinetics is provided by the coexpression of the β1 subunit, ubiquitously found in mammal tissues. This study uncovers the molecular bases responsible for the differential activation of Nav versus Kv channels, a fundamental prerequisite for the genesis of action potentials.
authors: Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57(th) Chicago, IL 60637, USA.
authors: Jérôme J
authors: JJ
authors: Lacroix
authors: Fabiana V
authors: FV
authors: Campos
authors: Ludivine
authors: L
authors: Frezza
authors: Francisco
authors: F
authors: Bezanilla
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena / Q000235:genetics; D004558:Electric Stimulation; D015640:Ion Channel Gating / Q000235:genetics*; D007700:Kinetics; D008845:Microinjections; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics*; D011487:Protein Conformation; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels
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