医三中三组织生理整合课程

1、 醫三中三組織生理整合課程 96學年度第1 學期 How Neurons Talk to Each Other? 林靜茹老師 Ext. 2189Synaptic Transmission 2007/10/30I. History Synapses（突觸）:Where neurons talkSynapse: First introduced by English Physiologist Charles Sherrington (Nobel Price in 1932) to describe contacts between neurons.Synaptic transmission: th

2、e process of information transfer at a synapse.1959: Edwin Furshpan and David Potter (American) - electrical synapses1921: Otto Loewi (Austria) Discovery of neurotransmitter- Ach (Nobel Laureate in 1936) - chemical synapsesSynaptic transmission in CNS: John Eccles (Nobel Laureate in 1963) -chemical

3、synapsesSynaptic transmission at Neuromuscular junction (NMJ): Benard Katz (Nobel Laureate in 1970) - chemical synapsesII. Types of Synapses (A). Electrical synapses: (from “Neuroscience: exploring the brain” 2nd edition)Gap junctions - cells share both electrical and chemical signals (bi-directiona

4、l) - cells are electrically coupled e.g. invertebrate: escape reflexes; vertebrate: glia, epithelial cells, smooth and cardiac muscle cells and liver cells(B). Chemical Synapses: need neurotransmitters (神經傳遞物質) for transmission, influenced by drugs, account for 99% of the synapses. (i). Neuromuscula

5、r junction (NMJ): a typical chemical synapse at PNS (Ganong Fig. 4-35) (ii). At CNS: (Vander Fig. 6-25)Three parts:a. The terminal of presynaptic axon（突觸前神經末梢）l synaptic vesicles l large dense core vesiclesb. The postsynaptic membrane under the axon terminal（突觸後膜） receptors active zonec. The synapti

6、c cleft（突觸裂隙）: 10-20 nm Unidirectional , synaptic delayIII. Mechanisms of neurotransmitter release (突觸訊號傳遞過程及機制)Vander Fig 6-27(A). Neurotransmitter release: Arrival of action potential at axonal terminals (depolarization) Voltage-gated calcium channels open Voltage-gated calcium channels open Neuro

7、transmitters released by exocytosis Neurotransmitters released by exocytosis Open or close ion channels; or G-protein coupled events Postsynaptic membrane potential changes (EPSP or IPSP)(B). The release of neurotransmitters by exocytosis. Vander Fig. 6-27 and Ganong Fig. 4-5 1). Vesicle docking:- S

8、NARES proteins Clostridium botulinum - botulism - Synaptotagmin2). Ca+ influx3). Neurotransmitters release 4). Membrane recycled by endocytosisIV. Activation of the postsynaptic cells Terms for membrane potential changes: depolarization, overshoot, repolarization, hyperpolarization, resting membrane

9、 potential (Vander Fig. 6-14); EPSP and IPSPAt the post-synaptic membrane (Vander fig. 6-28 and fig. 6-29): Depolarization occurs - Excitatory Post-Synaptic Potential (EPSP) Hyperpolarization occurs - Inhibitory Post-Synaptic potential (IPSP)Axon hillock- initial segment - lowest threshold Action po

10、tential (動作電位); Graded potential (漸進電位; Vander fig. 6-16)* Synaptic integration (synaptic summation 加成 or 總合)： Vander Figs. 6-24: Many-to-one (convergence; 匯聚) One-to-many (divergence; 分散); one-to-oneThe net post-synaptic membrane potential changes depend on the summation of all synaptic activities

11、affecting the postsynaptic neuron at that time window. * Spatial summation (空間的總合,Vander fig. 6-31; also Ganong fig. 4-7 A-C): two separate inputs arrive almost simultaneously* Temporal summation (時間的總合; Vander fig. 6-31; also Ganong fig. 4-7 D-F): when two or more action potentials in a single pres

12、ynaptic neuron occur in rapid succession, so the resultant post-synaptic potentials overlap in time. *Facilitation (Ganong fig. 4-11): when a presynaptic axon is stimulated repeatedly, the postsynaptic response may increase with each stimulation. (e.g. long-term potentiation in learning and memory)*

13、Synaptic fatigue - when a presynaptic axon is stimulated repeatedly for a long time - smaller postsynaptic response. V. Neurotransmitters and neuromodulators (Vander Table 6-7)1. Acetylcholine (Ach，乙醯膽鹼類)：cholinergic neurons defects- Alzheimers diseaseReceptors for Ach：A. Nicotinic receptors: recept

14、ors respond to both Ach and nicotine；ion channels; curare as antagonist (blocker)B. Muscarinic receptors：receptors respond to both Ach and muscarine； coupled with G proteins; atropine as antagonist (blocker)a. Agonist （催動劑）： drugs that binds to receptors and produces a similar response of the normal

15、 receptor activationb. Antagonist（結抗劑）： drugs that bind to receptors and are unable to activate it. Eg. Curare as nicotinic receptor blocker; Atropine as muscarinic receptor blockerAchE: Acetylcholinesterase (乙醯膽鹼酯化酵素) AchE inhibitor : nerve gas or insecticides - decrease in heart rate and blood pre

16、ssure, respiratory paralysis.2. Biogenic Amines（醯胺類）: Vander fig. 6-35; Ganong Fig. 4-21; 4-25Catecholamine biosynthesis pathway: Receptors for norepinephrine and epinephrine： receptors and receptors.Serotonin (血清張力素): synthesized from tryptophan, depression 3. Amino acids（胺基酸類）a. excitatory amino a

17、cid：glutamate（麩胺酸鹽）、aspartate（天門冬酸鹽）i). Ionotropic glutamate receptor: ion channels (Vander fig. 6-36; Ganong Fig. 4-28 and 4-34)ii). Metabotropic glutamate receptor: G-protein coupledb. inhibitatory amino acid：-GABA（-丁胺酸; Ganong Fig. 4-29）、glycine（甘胺酸）4. Neuropeptides or peptides（胜肽）Ganong Table 4-

18、4, 4-5 and fig. 4-305. Others: pyrimidine, purines, gases, lipidsVII. Modification of synaptic transmission by drugs (synaptic strength)Vander Fig. 6-34a). Increase leakage of neurotransmitters from vesicle to cytoplasmenzymatic breakdownb). Increase transmitter release into cleftc). Block transmitter release d). Inhibit transmitter synthesise). Block transmitter reuptakef). Block cleft enzyme that metabolize transmitterg). Bind to receptor on post-synaptic membrane to block or mimic transmitter actionh). Inhibit or facilitate