title: A novel fast mechanism for GPCR-mediated signal transduction--control of neurotransmitter release.
abstract: Reliable neuronal communication depends on accurate temporal correlation between the action potential and neurotransmitter release. Although a requirement for Ca(2+) in neurotransmitter release is amply documented, recent studies have shown that voltage-sensitive G protein-coupled receptors (GPCRs) are also involved in this process. However, how slow-acting GPCRs control fast neurotransmitter release is an unsolved question. Here we examine whether the recently discovered fast depolarization-induced charge movement in the M(2)-muscarinic receptor (M(2)R) is responsible for M(2)R-mediated control of acetylcholine release. We show that inhibition of the M(2)R charge movement in Xenopus oocytes correlated well with inhibition of acetylcholine release at the mouse neuromuscular junction. Our results suggest that, in addition to Ca(2+) influx, charge movement in GPCRs is also necessary for release control.
authors.affiliation: Department of Neurobiology, Institute of Life Sciences, Hebrew University, Jerusalem, Israel.
authors.forename: Yonatan M
authors.initials: YM
authors.lastname: Kupchik
authors.forename: Ofra
authors.initials: O
authors.lastname: Barchad-Avitzur
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wess
authors.forename: Yair
authors.initials: Y
authors.lastname: Ben-Chaim
authors.forename: Itzchak
authors.initials: I
authors.lastname: Parnas
authors.forename: Hanna
authors.initials: H
authors.lastname: Parnas
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005703:Gallamine Triethiodide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010782:Photolysis / Q000187:drug effects; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014981:Xenopus
chemical_list: D018377:Neurotransmitter Agents; D043585:Receptor, Muscarinic M2; D002217:Carbachol; D000109:Acetylcholine; D005703:Gallamine Triethiodide; D002118:Calcium