ArticleProceedings of the National Academy of Sciences of the United States of America2016
Unique pH dynamics in GABAergic synaptic vesicles illuminates the mechanism and kinetics of GABA loading.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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35 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
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- An Open-Science Computational Model of Organelle Acidification to Integrate Putative Mechanisms of Synaptic Vesicle Acidification and Filling.Neurochemical research · 2025Article
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- Mice lacking acid-sensing ion channel 2 in the medial prefrontal cortex exhibit social dominance.Science advances · 2024Article
- Glutamate Spillover Dynamically Strengthens Gabaergic Synaptic Inhibition of the Hypothalamic Paraventricular Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Dynamics of γ-aminobutyric acid concentration in the human brain in response to short visual stimulation.Magma (New York, N.Y.) · 2024Article
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- SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission.Brain : a journal of neurology · 2023Article
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- GABA tone regulation and its cognitive functions in the brain.Nature reviews. Neuroscience · 2023Review
- Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain.Biomolecules · 2023Article
- pH Effects Can Dominate Chemical Shift Perturbations inACS chemical neuroscience · 2023Article
- pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity.Frontiers in cellular neuroscience · 2023Article
- Diversity of function and mechanism in a family of organic anion transporters.Current opinion in structural biology · 2022Review
- Spontaneously Recycling Synaptic Vesicles Constitute Readily Releasable Vesicles in Intact Neuromuscular Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Article
- Quantitative Analysis of Presynaptic Vesicle Luminal pH in Cultured Neurons.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA acts as the major inhibitory neurotransmitter in the mammalian brain, shaping neuronal and circuit activity. For sustained synaptic transmission, synaptic vesicles (SVs) are required to be recycled and refilled with neurotransmitters using an H(+) electrochemical gradient. However, neither the mechanism underlying vesicular GABA uptake nor the kinetics of GABA loading in living neurons have been fully elucidated. To characterize the process of GABA uptake into SVs in functional synapses, we monitored luminal pH of GABAergic SVs separately from that of excitatory glutamatergic SVs in cultured hippocampal neurons. By using a pH sensor optimal for the SV lumen, we found that GABAergic SVs exhibited an unexpectedly higher resting pH (∼6.4) than glutamatergic SVs (pH ∼5.8). Moreover, unlike glutamatergic SVs, GABAergic SVs displayed unique pH dynamics after endocytosis that involved initial overacidification and subsequent alkalization that restored their resting pH. GABAergic SVs that lacked the vesicular GABA transporter (VGAT) did not show the pH overshoot and acidified further to ∼6.0. Comparison of luminal pH dynamics in the presence or absence of VGAT showed that VGAT operates as a GABA/H(+) exchanger, which is continuously required to offset GABA leakage. Furthermore, the kinetics of GABA transport was slower (τ > 20 s at physiological temperature) than that of glutamate uptake and may exceed the time required for reuse of exocytosed SVs, allowing reuse of incompletely filled vesicles in the presence of high demand for inhibitory transmission.
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