KCNQ2 but not KNCQ3, is expressed on neuronal axons, where it might regulate action potential propagation or neurotransmitter release. Previously, we showed that Syntaxin 1A physically interacts with homomeric KCNQ2 in brain synaptosomes and in Xenopus oocytes. In oocytes, this interaction results in a reduction of the current's amplitude and reduction of the channel's activation rate. In vitro pull down revealed that Syntaxin 1A specifically binds the Helix A domain located in the C-terminus of both KCNQ2 and KCNQ3. However, binding of Syntaxin to Helix A does not mediate Syntaxin's effect on the channel. We propose that the N-trminus of KCNQ2 plays a major role in the syntaxin's modulation since substitution of the proximal N-terminus of KCNQ2 with that of KCNQ3 abolished this effect. Since the effect of syntaxin 1A is mediated through the N-terminus we assume that the N-C termini of the channel interact. To study this hypothesis we used florescence resonance energy transfer (FRET) experiments, single channel analysis and biochemical approaches using chimeric channels. Together, our results point toward an allosteric modulation of KCNQ2 gating by Syntaxin 1A, facilitated by N-C termini interaction. 2316-Pos Board B302Slowing of Instantaneous Inactivation Causes Macroscopic Current Decay in Kv7.1 Alanine Mutants Vitya Vardanyan, Lijuan Ma, Olaf Pongs. Alanine scanning mutagenesis in Kv7.1 S4-S5 linker and the pore region revealed mutant channels with fast current decay at permanent depolarizing pulses above 10mV. It has been previously shown that such a macroscopic inactivation of many Kv7.1 pore mutants occurs in parallel to instantaneous inactivation of Kv7.1 channel. We have chosen four mutant channels I268A, G269A, F339A and F340A with most pronounced current decays to investigate the molecular mechanism underling decay process. Inactivation of these channels could not be explained by intracellular Naþ block reported earlier for Kv7.1 wild type channel. The fast current decay kinetics significantly changed neither by varying the extracellular Kþ concentration nor by replacement of the Kþ with equimolar Rbþ. Recovery from inactivation showed fast and slow components. The slow component was accelerated at high extracellular Kþ conditions, whereas the fast component did not change significantly. Our data suggest that instantaneous inactivation of wild type Kv7.1 channel markedly slowed by above mentioned alanine mutations resulting in macroscopic decay of current during prolonged depolarization.