title: Modulation of the K(v)4.3 channel by syntaxin 1A.
abstract: The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K(+) channels of the K(v)1 and K(v)2 families with heterogeneous effects on their gating properties. In this study, we explored whether Syn1A could directly modulate K(v)4.3, a rapidly inactivating K(v) channel with important roles in neuroendocrine cells and cardiac myocytes. Immunoprecipitation studies in HEK293 cells coexpressing Syn1A and K(v)4.3 revealed a direct interaction with increased trafficking to the plasma membrane without a change in channel synthesis. Paradoxically, Syn1A inhibited K(v)4.3 current density. In particular, Syn1A produced a left-shift in steady-state inactivation of K(v)4.3 without affecting either voltage dependence of activation or gating kinetics, a pattern distinct from other K(v) channels. Combined with our previous reports, our results further verify the notion that the mechanisms involved in Syn1A-K(v) interactions vary significantly between K(v) channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Ahmed
authors.forename: Laura I
authors.initials: LI
authors.lastname: Cosen-Binker
authors.forename: Yuk M
authors.initials: YM
authors.lastname: Leung
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Diamant
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D007700:Kinetics; D011188:Potassium / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051672:Shal Potassium Channels / Q000737:chemistry*; D013347:Subcellular Fractions; D050827:Syntaxin 1 / Q000737:chemistry / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D051672:Shal Potassium Channels; D050827:Syntaxin 1; D011188:Potassium