Modulation of the Kv4.3 channel by syntaxin 1A

The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K+ channels of the Kv1 and Kv2 families with heterogeneous effects on their gating properties. In this study, we explored whether Syn1A could directly modulate Kv4.3, a rapidly inactivating Kv channel with important roles in neuroendocrine cells and cardiac myocytes. Immunoprecipitation studies in HEK293 cells coexpressing Syn1A and Kv4.3 revealed a direct interaction with increased trafficking to the plasma membrane without a change in channel synthesis. Paradoxically, Syn1A inhibited Kv4.3 current density. In particular, Syn1A produced a left-shift in steady-state inactivation of Kv4.3 without affecting either voltage dependence of activation or gating kinetics, a pattern distinct from other Kv channels. Combined with our previous reports, our results further verify the notion that the mechanisms involved in Syn1A–Kv interactions vary significantly between Kv channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability.