title: Proton electrochemical gradient: Driving and regulating neurotransmitter uptake.
abstract: Accumulation of neurotransmitters in the lumen of synaptic vesicles (SVs) relies on the activity of the vacuolar-type H+-ATPase. This pump drives protons into the lumen, generating a proton electrochemical gradient (ΔμH+) across the membrane. Recent work has demonstrated that the balance between the chemical (ΔpH) and electrical (ΔΨ) components of ΔμH+is regulated differently by some distinct vesicle types. As different neurotransmitter transporters use ΔpH and ΔΨ with different relative efficiencies, regulation of this gradient balance has the potential to influence neurotransmitter uptake. Nevertheless, the underlying mechanisms responsible for this regulation remain poorly understood. In this review, we provide an overview of current neurotransmitter uptake models, with a particular emphasis on the distinct roles of the electrical and chemical gradients and current hypotheses for regulatory mechanisms.
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Farsi
authors.affiliation: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Woehler
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D004563:Electrochemistry; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017494:Proton Pumps / Q000378:metabolism*; D011522:Protons; D013572:Synaptic Vesicles / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D017494:Proton Pumps; D011522:Protons; D018698:Glutamic Acid; D025262:Vacuolar Proton-Translocating ATPases
keywords: buffering capacity; ion-proton exchangers; neurotransmitter uptake; proton electrochemical gradient; proton pump; vesicular transporters