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Loewi's experiment demonstrating chemical neurotransmission. (A) Diagram of experimental setup. (B) Where the vagus nerve of an isolated frog's heart was.

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Presentation on theme: "Loewi's experiment demonstrating chemical neurotransmission. (A) Diagram of experimental setup. (B) Where the vagus nerve of an isolated frog's heart was."— Presentation transcript:

1 Loewi's experiment demonstrating chemical neurotransmission. (A) Diagram of experimental setup. (B) Where the vagus nerve of an isolated frog's heart was stimulated, the heart rate decreased (upper panel). If the perfusion fluid from the stimulated heart was transferred to a second heart, its rate decreased as well (lower panel).

2 Demonstrating the identity of a neurotransmitter at a synapse requires showing (1) its presence, (2) its release, and (3) the postsynaptic presence of specific receptors.

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5 Oxyde nitrique Les amines biogènes Acides aminés Peptides Others AcetylcholineMonoamines SérotonineCatécholamine Noradrénaline Dopamine Adrénaline Substance P ATPGlutamateGABA Neurotransmetteurs à petites molécules

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11 B) Small-molecule neurotransmitters are synthesized at nerve terminals. The enzymes necessary for neurotransmitter synthesis are made in the cell body of the presynaptic cell (1) and are transported down the axon by slow axonal transport (2). Precursors are taken up into the terminals by specific transporters, and neurotransmitter synthesis and packaging take place within the nerve endings (3). After vesicle fusion and release (4), the neurotransmitter may be enzymatically degraded. The reuptake of the neurotransmitter (or its metabolites) starts another cycle of synthesis, packaging, release, and removal (5).

12 (C) Peptide neurotransmitters, as well as the enzymes that modify their precursors, are synthesized in the cell body (1). Enzymes and propeptides are packaged into vesicles in the Golgi apparatus. During fast axonal transport of these vesicles to the nerve terminals (2), the enzymes modify the propeptides to produce one or more neurotransmitter peptides (3). After vesicle fusion and exocytosis, the peptides diffuse away and are degraded by proteolytic enzymes (4).

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26 M1M1 M2M2 M3M3 M4M4 M5M5 Distribution Cortex, hippocampus Heart Exocrine glands, GI tract Neostriatum Substantia nigra G protein G  q/11 G  i/o G  q/11 G  i/o G  q/11 Intracellular response Phospholipase C  Action stimulante Adenylyl cyclase inhibition Phospholipase C  Action stimulante Adenylyl cyclase inhibition Phospholipa se C 

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28 Acetylcholine metabolism in cholinergic nerve terminals. The synthesis of acetylcholine from choline and acetyl CoA requires choline acetyltransferase. Acetyl CoA is derived from pyruvate generated by glycolysis, while choline is transported into the terminals via a Na+-dependent transporter. After release, acetylcholine is rapidly metabolized by acetylcholinesterase and choline is transported back into the terminal.

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30 Conditions ioniques Intérieur 160 mM K, 3 Na, 163 Cl- Extérieur 160 Na, 3 K, 165 Cl- 5- action nicotinique 5.1 proprietes des récepteurs nicitiniques

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33 Current evoked by nicotine in cultured rat superior cervical ganglia. The cell membrane potentials were held at _70 mV.

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35 Name: Curare Genus: Chondrodendron Species: tomtosum

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37 Series of endplate potentials/action potentials in frog muscle under the increasing effect of a concentration of tubocurarine added at b. As endplate potential falls below threshold, action potential fails and there is no mechanical response. Series summarized in h.

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40 Clostridium botulinum Acétyl choline GABA

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42 Traitement de la myasténie grave

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46 ReceptorTissueResponse Muscarinic (M1)Smooth muscles and glands of the gut Smooth muscle contraction and glandular secretion (relatively slow response) Muscarinic (M2)Smooth and cardiac muscle of cardiovascular system Smooth muscle contraction; some inotropic effect on cardiac muscle Muscarinic (M3)Smooth muscles and glands of all targets Smooth muscle contraction, glandular secretion

47 Potentiel d’action ACh Ca 2+ ATP ADP Na + Ca 2+ Na + K+K+ K+K+  AC AMPc ATP R M 2 - =

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52 Belladona : (Atropa belladona)

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55 6- action muscarinique 6.4 la muscarine agoniste Amanita muscaria Troubles digestifs Sueurs profuses, hypersecrétion bronchique et salivaire bradycardie et hypotension myosis Traitement spécifique=administration IV d’atropine ttes les 15 min Apparition de symptômes en 30 min à 2H

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