Interaction of syntaxin with a single Kv1.1 channel: a possible mechanism for modulating neuronal excitability.
Voltage-gated K(+) channels are crucial for intrinsic neuronal plasticity and present a target for modulations by protein-protein interactions, notably, by exocytotic proteins demonstrated by us in several systems. Here, we investigated the interaction of a single Kv1.1 channel with syntaxin 1A. Syntaxin decreased the unitary conductance of all conductance states (two subconductances and a full conductance) and decreased their open probabilities by prolongation of mean closed dwell-times at depolarized potentials. However, at subthreshold potentials syntaxin 1A increased the probabilities of the subconductance states. Consequently, the macroscopic conductance is decreased at potentials above threshold and increased at threshold potentials. Numerical modeling based on steady-state and kinetic analyses suggests: (1) a mechanism whereby syntaxin controls activation gating by forcing the conductance pathway only via a sequence of discrete steps through the subconductance states, possibly via a breakdown of cooperative movements of voltage sensors that exist in Kv1.1; (2) a physiological effect, apparently paradoxical for an agent that reduces K(+) current, of attenuating neuronal firing frequency via an increase in K(+) shunting conductance. Such modulation of the gain of neuronal output in response to different levels of syntaxin is in accord with the suggested role for Kv1.1 in axonal excitability and synaptic efficacy.
Michaelevski
Izhak
I
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, 69978, Ramat-Aviv, Israel.
Korngreen
Alon
A
Lotan
Ilana
I
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D050827:Syntaxin 1; D029867:Xenopus Proteins; C084069:kcna1 protein, Xenopus; D051662:Kv1.1 Potassium Channel