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Functional impact of syntaxin on gating of N-type and Q-type calcium channels

Abstract

RAPID and reliable synaptic transmission depends upon the close proximity of voltage-gated calcium channels and neurotransmitter-containing vesicles in the presynaptic terminal1. Although it is clear that a local Ca2+ rise conveys the crucial signal from Ca2+ channels to the exocytotic mechanism2, little is known about whether communication ever proceeds in the opposite direction, from the release machinery to Ca2+ channels3,4. To look for such signalling, we examined the interaction of various types of voltage-gated Ca2+ channels with syntaxin, a presynaptic membrane protein of relative molecular mass 35,000 (refs 5–7) which may play a key part in synaptic vesicle docking and fusion8 and which interacts strongly with N-type Ca2+ channels5,6,9–12. Here we report that co-expression of syntaxin 1A with N-type channels in Xenopus oocytes sharply decreases the availability of these channels. This is due to the stabilization of channel inactivation rather than to a simple block or lack of channel expression, because it is overcome by strong hyperpolarization. Deletion of syntaxin's carboxy-terminal transmembrane domain abolishes its functional effect on Ca2+ channels. Syntaxin produced a similar effect on Q-type Ca2+ channels encoded by α1A (refs 13-15) but not on L-type Ca2+-channels. Thus, the syntaxin effect is specific for Ca2+ channel types that participate in fast transmitter release in the mammalian central nervous system (ref. 16 and therein). We hypothesize that, in addition to acting as a vesicle-docking site, syntaxin may influence presynaptic Ca2+ channels, opposing Ca2+ entry where it is not advantageous, but allowing it at release sites where synaptic vesicles have become docked and/or ready for fusion.

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Bezprozvanny, I., Scheller, R. & Tsien, R. Functional impact of syntaxin on gating of N-type and Q-type calcium channels. Nature 378, 623–626 (1995). https://doi.org/10.1038/378623a0

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