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Signal transmission at synapses Alice Skoumalová
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Page 1: Signal transmission at synapses Alice Skoumalová.

Signal transmission at synapses

Alice Skoumalová

Page 2: Signal transmission at synapses Alice Skoumalová.

Neurosecretions:

Neurotrasmitters x Neurohormones

released into the synaptic cleft

influence neighboring cells

a short lifespan

released into the blood

cover large distances

a longer lifespan

Page 3: Signal transmission at synapses Alice Skoumalová.

Synaptic signal transmission

Page 4: Signal transmission at synapses Alice Skoumalová.

Exocytosis process that allow cells to expel

substances (neurotransmitters, hormones)

secretory vesicles fuse with plasma membrane and release their contens

regulated by chemical or electrical signals

The resting state (synaptobrevin is blocked)

1. Voltage-gated Ca2+ channels open - Ca2+ flow in – conformational changes in proteins

2. Membrane fusion (supported by the hydrolysis of GTP by Rab protein)

Botulotoxine: destroys components of the exocytosis in synapses through enzymatic hydrolysis

Page 5: Signal transmission at synapses Alice Skoumalová.
Page 6: Signal transmission at synapses Alice Skoumalová.

Acetylcholine

1. The synthesis: from choline and acetyl-CoA in the neurons

2. Hydrolysis: in the synaptict cleft (restores the resting potential in the postsynaptic membrane)

- the transmitter of the parasympathetic and sympathetic system, at neuromuscular junctions, involved in learning and memory

Page 7: Signal transmission at synapses Alice Skoumalová.

Metabolism of acetylcholine

Page 8: Signal transmission at synapses Alice Skoumalová.

Acetylcholinesterase inhibitors

1. Reverzible:

therapeutic uses (myastenia gravis, Alzheimer disease)

carbamates (physostigmine, neostigmine)

2. Irreverzible:

have use as chemical weapons or pesticides

organophosphates (soman, sarin)

= inhibit acetylcholinesterase from breaking down acetylcholine, so increasing both the level and duration of action of the acetylcholine

Page 9: Signal transmission at synapses Alice Skoumalová.

Cholinergic synapses

Receptors nicotinic muscarinic

Mode of action ion channel G proteins:

GP GI

Presence the autonomic nervous system, neuromuscular junctions, adrenal medulla

brain, myocardium,

smooth muscles, brain

glands

Antagonists tubocurarine atropine

Page 10: Signal transmission at synapses Alice Skoumalová.

A transmembrane structure

- 5 subunits

- an ion por in the center

The nicotinic acetylcholine receptor

The sequence of the subunits

- 5 α-helixes traverse the membrane

Page 11: Signal transmission at synapses Alice Skoumalová.

Catecholamines

1 2 3 4

1. Hydroxylation of the aromatic ring: tetrahydrobiopterin, therapy of PD

2. Decarboxylation of dopa

3. Hydroxylation of dopamin: ascorbic acid

4. N-methylation of norepinephrine: S-adenosylmethionine

1. 2. 3. 4.

Page 12: Signal transmission at synapses Alice Skoumalová.

Catabolism of catecholamines

Clinical importance:

Pheochromocytoma:hypertension

metanephrines and vanillylmandelic acid in urine

Antidepressants: monoaminooxidase (MAO) inhibitors

SSRIs (specific serotonin reuptake inhibitors)

Page 13: Signal transmission at synapses Alice Skoumalová.

Adrenergic synapses

Receptors α1 α2 β1 β2

Mode of effect GP GI GS GS

Presence smooth muscles in GIT

(sphincters), scin vessels

pancreas myocardium smooth muscles in

bronchi, GIT (peristalsis)

Page 14: Signal transmission at synapses Alice Skoumalová.

GABA, glutamate

-synthesis in neurons

-re-uptake

1. neuroglia supply with glutamine

2.hydrolysis of glutamine to glutamate

3.decarboxylation to GABA

Clinical importance: -the Chinese restaurant syndrome (the monosodium glutamate – raise the glutamate level in the brain- neurological disturbances)

Page 15: Signal transmission at synapses Alice Skoumalová.

GABAA-receptor

- brain, spinal cord

GABA binds to the receptor

Cl- ions flow in

increase of the membrane´s resting potential (hinder the action of

stimulatory transmitters)

= hyperpolarization

Page 16: Signal transmission at synapses Alice Skoumalová.

Receptors for neurotransmitters