Handbook of Experimental Pharmacology Volume 184 pdf

[...]... thomas.feuerstein@uniklinik-freiburg.de Ralf Gilsbach Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany Jorge Gonalves Department of Pharmacology, Faculty of Pharmacy, University of Porto, Porto, Portugal, jgon¸alves@reit.up.pt c Lutz Hein Institute of Experimental and Clinical Pharmacology, University of Freiburg, Albertstrasse 25, 79104 Freiburg,... Center, Dallas, TX 75390-9111, USA thomas.sudhof@utsouthwestern.edu T.C S¨ dhof, K Starke (eds.), Pharmacology of Neurotransmitter Release u Handbook of Experimental Pharmacology 184 c Springer-Verlag Berlin Heidelberg 2008 1 2 T.C S¨ dhof u and gases such as endocannabinoids and nitric oxide Most of these transmitters are released by exocytosis, the i.e the fusion of secretory vesicles with the plasma membrane,... cesare.montecucco@unipd.it Gl´ ria Queiroz o Department of Pharmacology, Faculty of Pharmacy, University of Porto, Porto, Portugal, gloria@ff.up.pt M Raiteri Department of Experimental Medicine, Pharmacology and Toxicology Section, Center of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, Italy, raiteri@pharmatox.unige.it Alexis Rohou Division of Cell and Molecular Biology, Imperial College... dhof, K Starke (eds.), Pharmacology of Neurotransmitter Release u Handbook of Experimental Pharmacology 184 c Springer-Verlag Berlin Heidelberg 2008 23 24 M Khvotchev, E.T Kavalali can be detected biochemically, albeit on a time scale slower than electrophysiological methods In addition, in certain preparations, where presynaptic terminals are accessible to whole cell recording electrodes, fusion of. .. (1921), but the definitive description of these receptors was enabled by the simultaneous development of patch clamping by Neher and Sakmann (1976) and of molecular cloning of these receptors by S Numa (Noda et al., 1982) 3 Basic Mechanisms of Release by Exocytosis Most neurotransmitter release occurs by exocytosis of secretory vesicles, which involves the fusion of the secretory vesicles (synaptic vesicles... trains The kiss-andrun mode allows fast recycling of synaptic vesicles for reuse after exocytosis, but probably has only a minimal effect on the kinetics or amount of release because the total size of synaptic vesicles (∼20 nm radius) is only 5- to 10-fold larger than that of the fusion pore The definition of the primary structure of synaptotagmin-1, composed of an N-terminal transmembrane region and two... synaptic networks 5 Regulation of Release Beyond Ca2+ -Triggering We already alluded to the fact that release is not constant, but is highly plastic, i.e., regulated by extrinsic signals and by the intrinsic previous activity of a nerve terminal Both forms of regulation constitute a type of synaptic memory: the history of the activity of other surrounding neurons and of the neuron to which a terminal... different forms of synaptic plasticity exist Although traditionally postsynaptic forms of plasticity have been appreciated more than presynaptic forms, recent studies have revealed the existence of purely presynaptic forms of synaptic plasticity, and have moreover shown that many forms of plasticity are mediated by the combined action of preand postsynaptic mechanisms A complete discussion of presynaptic... presynaptic modulation and plasticity of release is beyond the scope of this chapter Instead, three exemplary forms of presynaptic plasticity will be discussed because of their importance for the pharmacology of neurotransmitter release 5.1 Acetylcholine-Receptor-Mediated Ca2+ -Influx into Presynaptic Nerve Terminals Nicotine is an addictive drug that activates a diverse subset of ionotropic acetylcholine receptors... Interestingly, this form of plasticity appears to depend on the interaction 18 T.C S¨ dhof u of the synaptic vesicle GTP-binding protein Rab3 with its effectors, RIM-proteins (Figure 3), since deletion of either Rab3A or of RIM1α abolishes LTP in the hippocampal mossy fibers (Castillo et al., 2002) Moreover, recently it was revealed that a special form of endocannabinoid-dependent long-term depression of GABAergic . USA thomas.sudhof@utsouthwestern.edu T.C. S ¨ udhof, K. Starke (eds.), Pharmacology of Neurotransmitter Release. 1 Handbook of Experimental Pharmacology 184. c  Springer-Verlag Berlin Heidelberg 2008 2 T.C. S ¨ udhof and gases. Queiroz Department of Pharmacology, Faculty of Pharmacy, University of Porto, Porto, Portugal, gloria@ff.up.pt M. Raiteri Department of Experimental Medicine, Pharmacology and Toxicology Section, Center of Excellence. alt="" Handbook of Experimental Pharmacology Volume 184 Editor-in-Chief K. Starke, Freiburg i. Br. Editorial Board S. Duckles, Irvine, CA M. Eichelbaum, Stuttgart D. Ganten, Berlin F. Hofmann,