title: Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion.
abstract: Neurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca(2+) channel activity, metabotropic GABA(B) receptors (GABA(B)Rs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABA(B)R agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABA(B)R activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABA(B)Rs can inhibit neurotransmitter release directly by increasing the energy barrier for vesicle fusion.
authors.affiliation: Neuroscience Research Centre, Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Rost
authors.forename: Patrick
authors.initials: P
authors.lastname: Nicholson
authors.forename: Gudrun
authors.initials: G
authors.lastname: Ahnert-Hilger
authors.forename: Andreas
authors.initials: A
authors.lastname: Rummel
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
authors.forename: Joerg
authors.initials: J
authors.lastname: Breustedt
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002478:Cells, Cultured; D060733:Electromagnetic Radiation; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000473:pathology; D050825:Synaptosomal-Associated Protein 25 / Q000037:antagonists & inhibitors
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D050825:Synaptosomal-Associated Protein 25; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA; D001418:Baclofen