Insertion of a SNS-specific tetrapeptide in S3-S4 linker of D4 accelerates recovery from inactivation of skeletal muscle voltage-gated Na channel mu1 in HEK293 cells.
Na channel subunits alphaSNS (PN3) and alpha mu1(SkM1) produce slowly inactivating/TTX-resistant and rapidly inactivating/TTX-sensitive currents, respectively. AlphaSNS (PN3) current recovers from inactivation (reprimes) rapidly. Sequence alignment identified the tetrapeptide SLEN, in the S3-S4 linker of D4, as alphaSNS-specific. To determine whether SLEN endows Na channels with slow kinetics and/or rapid repriming, we analyzed the transient Na current produced by a chimera mu1SLEN in HEK293 cells. Neither kinetics nor voltage dependence of activation and inactivation was affected. However, repriming was twice as fast as in the wild type at -100 mV. This suggests that SLEN may contribute to the rapid repriming of TTX-resistant Na current.
Dib-Hajj
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Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Ishikawa
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Cummins
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Waxman
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D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D016296:Mutagenesis; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009842:Oligopeptides; C568317:SCN10A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C023790:tetrodotoxin-binding protein