Modulation of the K(v)4.3 channel by syntaxin 1A |
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Authors: | Ahmed Ishtiaq Cosen-Binker Laura I Leung Yuk M Gaisano Herbert Y Diamant Nicholas E |
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Affiliation: | Department of Medicine, University of Toronto, Toronto, Canada. |
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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. |
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Keywords: | ATP, adenosine triphosphate CFTR, cystic fibrosis transmembrane conductance regulator HEK, human embryonic kidney Kv, voltage gated potassium channel KATP, ATP-sensitive K+ channel KCHIP, Kv channel interacting proteins SNAP-25, synaptosomal-associated protein-25 SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor Syn1A, syntaxin 1A Syn2, syntaxin 2 τact, activation time constant τinact, fast, fast inactivation time constant τinact, slow, slow inactivation time constant V1/2, half-maximal |
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