Syntaxin modulates Kv1.1 through dual action on channel surface expression and conductance

The Kv1.1 channel that is expressed throughout the central and peripheral nervous system is known to interact with syntaxin 1A, a member of the exocytosis machinery protein complex. This interaction was previously shown to increase the macroscopic currents of the presynaptic Kv1.1 channel when coexpressed in Xenopus oocytes, while it decreased the unitary channel conductance and open probability. This apparent discrepancy has been resolved in this work, using electrophysiological, biochemical, and immunohistochemical analyses in oocytes by overexpression and antisense knockdown of syntaxin. Here, we demonstrate that syntaxin plays a dual role in the modulation of Kv1.1 function: enhancement of the channel's surface expression along with attenuation of single channel ion flux. These findings broaden the scope of channels and transporters that are dually modulated by syntaxin. Although the dual functioning of syntaxin in modulation of Kv1.1 channel activity may seem antagonistic, the combination of the two mechanisms may provide a useful means for fine-tuning axonal excitability and synaptic efficacy.