Department of Physiology, Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
Nat Neurosci. 2011 Aug 28;14(10):1285-92. doi: 10.1038/nn.2898.
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 are poorly understood. A proton electrochemical gradient (Δμ(H+)) generated by the vacuolar H(+)-ATPase drives the accumulation of classical transmitters into synaptic vesicles. The chemical component of Δμ(H+) (ΔpH) has received particular attention for its role in the vesicular transport of cationic transmitters as well as in 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 Δμ(H+) (Δψ). We found that rat brain synaptic vesicles express monovalent cation/H(+) exchange activity that converts ΔpH into Δψ, and that this promotes synaptic vesicle filling with glutamate. Manipulating presynaptic K(+) at a glutamatergic synapse influenced quantal size, indicating that synaptic vesicle K(+)/H(+) exchange regulates glutamate release and synaptic transmission.
单个突触囊泡中储存的神经递质的量可以决定突触后反应的大小，但调节囊泡填充的因素知之甚少。液泡 H(+)-ATP 酶产生的质子电化学梯度 (Δμ(H+)) 驱动经典递质积累到突触囊泡中。Δμ(H+) 的化学成分 (ΔpH) 因其在阳离子递质的囊泡运输以及蛋白质分拣和降解中的作用而受到特别关注。因此，大量工作已经解决了促进 ΔpH 的因素。然而，主要兴奋性递质谷氨酸的突触囊泡摄取依赖于 Δμ(H+) 的电成分 (Δψ)。我们发现，大鼠脑突触囊泡表达单价阳离子/H(+)交换活性，将 ΔpH 转化为 Δψ，这促进了谷氨酸的突触囊泡填充。在谷氨酸能突触处操纵突触前 K(+) 会影响量子大小，表明突触囊泡 K(+)/H(+) 交换调节谷氨酸释放和突触传递。
