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Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion

Item Type:Article
Title:Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion
Creators Name:Rost, B.R. and Nicholson, P. and Ahnert-Hilger, G. and Rummel, A. and Rosenmund, C. and Breustedt, J. and Schmitz, D.
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.
Keywords:GABA-B Receptor, Metabotropic, Neurotransmission, Energy Barrier, SNARE, Presynaptic Inhibition, Animals, Mice, Rats
Source:Journal of Cell Science
ISSN:0021-9533
Publisher:Company of Biologists (U.K.)
Volume:124
Number:Pt 18
Page Range:3066-3073
Date:15 September 2011
Official Publication:https://doi.org/10.1242/jcs.074963
PubMed:View item in PubMed

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