title: Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport.
abstract: 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.
authors.affiliation: Department of Physiology, Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Germaine Y
authors.initials: GY
authors.lastname: Goh
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Julie
authors.initials: J
authors.lastname: Ullman
authors.forename: Lars
authors.initials: L
authors.lastname: Borre
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hnasko
authors.forename: Laurence O
authors.initials: LO
authors.lastname: Trussell
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D060829:Arthropod Proteins; D001224:Aspartic Acid / Q000493:pharmacokinetics; D001692:Biological Transport; D055592:Biophysical Phenomena / Q000187:drug effects; D001921:Brain / Q000166:cytology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005942:Gluconates / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial; D008985:Monensin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D012975:Sodium Isotopes / Q000493:pharmacokinetics; D013569:Synapses / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000648:ultrastructure; D014316:Tritium / Q000493:pharmacokinetics; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D060829:Arthropod Proteins; D002412:Cations; D005942:Gluconates; D007476:Ionophores; D009842:Oligopeptides; D012975:Sodium Isotopes; D050496:Vesicular Glutamate Transport Proteins; C089492:glycyl-histidyl-seryl-leucyl-leucyl-histidyl-phenylalaninamide; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000584:Amiloride; D008985:Monensin; C030691:gluconic acid; D011188:Potassium; C039614:ethylisopropylamiloride