Single-vesicle imaging reveals different transport mechanisms between glutamatergic and GABAergic vesicles

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Science  11 Feb 2016:
DOI: 10.1126/science.aad8142

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Synaptic transmission is mediated by the release of neurotransmitters, which involves exo-endocytotic cycling of synaptic vesicles. To maintain synaptic function, synaptic vesicles are re-filled with thousands of neurotransmitter molecules within seconds after endocytosis, using the energy provided by an electrochemical proton gradient. However, it is unclear how transmitter molecules carrying different net charges can be efficiently sequestered while maintaining charge neutrality and osmotic balance. Here we used single-vesicle imaging to monitor pH and electrical gradients and directly showed different uptake mechanisms for glutamate and GABA operating in parallel. In contrast to glutamate, GABA was exchanged for protons, with no other ions participating in the transport cycle. Thus, only a few components are needed to guarantee reliable vesicle filling with different neurotransmitters.

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