title: Interaction between fast and slow inactivation in Skm1 sodium channels.
abstract: Rat skeletal muscle (Skm1) sodium channel alpha and beta 1 subunits were coexpressed in Xenopus oocytes, and resulting sodium currents were recorded from on-cell macropatches. First, the kinetics and steady-state probability of both fast and slow inactivation in Skm1 wild type (WT) sodium channels were characterized. Next, we confirmed that mutation of IFM to QQQ (IFM1303QQQ) in the DIII-IV 'inactivation loop' completely removed fast inactivation at all voltages. This mutation was then used to characterize Skm1 slow inactivation without the presence of fast inactivation. The major findings of this paper are as follows: 1) Even with complete removal of fast inactivation by the IFM1303QQQ mutation, slow inactivation remains intact. 2) In WT channels, approximately 20% of channels fail to slow-inactivate after fast-inactivating, even at very positive potentials. 3) Selective removal of fast inactivation by IFM1303QQQ allows slow inactivation to occur more quickly and completely than in WT. We conclude that fast inactivation reduces the probability of subsequent slow inactivation.
authors.affiliation: Department of Biology, Utah State University, Logan 84322-5305, USA. davef@cc.usu.edu
authors.forename: D E
authors.initials: DE
authors.lastname: Featherstone
authors.forename: J E
authors.initials: JE
authors.lastname: Richmond
authors.forename: P C
authors.initials: PC
authors.lastname: Ruben
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D046911:Macromolecular Substances; D011994:Recombinant Proteins; D015222:Sodium Channels