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?
Synaptic Transmission
林靜茹老師 Ext. 2189
2007/10/30
I.
History
Synapses（突觸）:Where neurons talk
Synapse: First introduced by English Physiologist Charles Sherrington (Nobel Price
in 1932) to describe contacts between neurons.
Synaptic transmission: the process of information transfer at a synapse.
1959: Edwin Furshpan and David Potter (American) ---- electrical synapses
1921: Otto Loewi (Austria) Discovery of neurotransmitter- Ach (Nobel Laureate in
1936) --- chemical synapsesSynaptic transmission in CNS: John Eccles (Nobel
Laureate in 1963) ---chemical synapses
Synaptic transmission at Neuromuscular junction (NMJ): Benard Katz (Nobel
Laureate in 1970) --- chemical synapses
II.
Types of Synapses
(A). Electrical synapses: (from “Neuroscience: exploring the brain” 2nd edition)
Gap junctions --- cells share both electrical and chemical signals (bi-directional) --cells are electrically coupled
e.g. invertebrate: escape reflexes;
vertebrate: glia, epithelial cells, smooth and cardiac muscle cells and liver cells
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(B). Chemical Synapses: need neurotransmitters (神經傳遞物質) for transmission,
influenced by drugs, account for 99% of the synapses.
(i). Neuromuscular 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）
 synaptic vesicles
 large dense core vesicles
b. The postsynaptic membrane under the axon terminal（突觸後膜）
●
receptors
active zone
c. The synaptic cleft（突觸裂隙）: 10-20 nm
●
●Unidirectional
III.
, synaptic delay
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
Neurotransmitters 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:
-- SNARES proteins
Clostridium botulinum -- botulism
-- Synaptotagmin
2). Ca++ influx
3). Neurotransmitters release
4). Membrane recycled by endocytosis
IV. Activation of the postsynaptic cells
Terms for membrane potential changes: depolarization, overshoot, repolarization,
hyperpolarization, resting membrane potential (Vander Fig. 6-14); EPSP and
IPSP
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At 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 potential (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-one
The net post-synaptic membrane potential changes depend on the summation of all
synaptic activities 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 presynaptic
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)
*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--- Alzheimer’s disease
Receptors for Ach：
A. Nicotinic receptors: receptors 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 receptor activation
b. 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 blocker
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AchE: Acetylcholinesterase (乙醯膽鹼酯化酵素)
AchE inhibitor : nerve gas or insecticides --- decrease in heart rate and blood
pressure, respiratory paralysis.
2. Biogenic Amines（醯胺類）: Vander fig. 6-35; Ganong Fig. 4-21; 4-25
Catecholamine biosynthesis pathway:
Receptors for norepinephrine and epinephrine：
α receptors and β receptors.
Serotonin (血清張力素): synthesized from tryptophan, depression
3. Amino acids（胺基酸類）
a. excitatory amino acid：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 coupled
b. inhibitatory amino acid：γ-GABA（γ-丁胺酸; Ganong Fig. 4-29）、
glycine（甘胺酸）
4. Neuropeptides or peptides（胜肽）Ganong Table 4-4, 4-5 and fig. 4-305. Others:
pyrimidine, purines, gases, lipids
VII. Modification of synaptic transmission by drugs (synaptic strength)
Vander Fig. 6-34
a). Increase leakage of neurotransmitters from vesicle to cytoplasm—enzymatic
breakdown
b). Increase transmitter release into cleft
c). Block transmitter release
d). Inhibit transmitter synthesis
e). Block transmitter reuptake
f). Block cleft enzyme that metabolize transmitter
g). Bind to receptor on post-synaptic membrane to block or mimic transmitter action
h). Inhibit or facilitate secondary messenger activity within postsynaptic cell.
References:
1).Vander’s “Human Physiology” 10th edition. Ch. 6
2). W.F. Ganong “Review of Medical Physiology” 22th edition. 2005
3). Bear, M.F., Connor, B.W. and Paradiso M.A. "Neuroscience: exploring
the brain", 2nd edition. Chs. 5-6.
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