Modulation of the K(v)4.3 channel by syntaxin 1A.
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.
Ahmed
Ishtiaq
I
Department of Medicine, University of Toronto, Toronto, Canada.
Cosen-Binker
Laura I
LI
Leung
Yuk M
YM
Gaisano
Herbert Y
HY
Diamant
Nicholas E
NE
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
D018076:DNA, Complementary; D051672:Shal Potassium Channels; D050827:Syntaxin 1; D011188:Potassium