Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport.

Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport.
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DOI:
10.1038/nn.2898
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发表时间:
2011-08-28
影响因子:
25
通讯作者:
Edwards RH
Edwards RH
中科院分区:
医学1区
文献类型:
--
作者:
Goh GY;Huang H;Ullman J;Borre L;Hnasko TS;Trussell LO;Edwards RH

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储存在单个突触囊泡中的神经递质的量可以决定突触后反应的大小,但是调节囊泡填充的因素仍然知之甚少。由液泡H+-ATP酶产生的质子电化学梯度(ΔμH+)驱动经典递质聚集到突触囊泡中。ΔμH+(ΔpH)的化学成分因其在阳离子递质的囊泡转运以及蛋白质分选和降解中的作用而受到特别关注。因此,大量的工作已经解决了促进ΔpH的因素。然而,突触囊泡对主要兴奋性递质谷氨酸的摄取依赖于ΔμH+(Δ μH+)的电成分。我们现在发现,大鼠脑突触囊泡表达单价阳离子/H+交换活性,将ΔpH转化为Δ pH,这促进了突触囊泡充满谷氨酸。操纵突触前K+在谷氨酸能突触影响量子大小,表明突触囊泡K+/H+交换调节谷氨酸释放和突触传递。
The amount of neurotransmitter stored in a single synaptic vesicle can determine the size of the postsynaptic response, but the factors that regulate vesicle filling remain poorly understood. A proton electrochemical gradient (ΔμH+) generated by the vacuolar H+-ATPase drives the accumulation of classical transmitters into synaptic vesicles. The chemical component of ΔμH+ (ΔpH) has received particular attention for its role in the vesicular transport of cationic transmitters as well as protein sorting and degradation. Thus, considerable work has addressed the factors that promote ΔpH. However, synaptic vesicle uptake of the principal excitatory transmitter glutamate depends on the electrical component of ΔμH+ (Δψ). We now find that rat brain synaptic vesicles express monovalent cation/H+ exchange activity that converts ΔpH into Δψ, and this promotes synaptic vesicle filling with glutamate. Manipulating presynaptic K+ at a glutamatergic synapse influences quantal size, demonstrating that synaptic vesicle K+/H+ exchange regulates glutamate release and synaptic transmission.
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