the synaptic transmission m.bayat phd
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The Synaptic transmission M.Bayat PhD
Session 4 The Synaptic transmission M.Bayat PhD The Sanger
Institute http://highered. mcgraw-hill
Two principal kinds of synapses: electrical and chemical
Where nerve impulses convert to neurotransmitters Gap junctions are
formed where hexameric pores called connexons connect with one
between cells Electrical Synapses Allows the direct transfer of
ionic current from one cell to the next. Gap Junction is composed
of 6 connexins that make up a connexon. (Pore size = 2nm) Ions can
flow bidirectionally. Cells are electronically coupled. Conduction
speed is very fast. Found in neuronal pathways associated with
escape reflexes or in neurons that need to be synchronized. Common
in non neuronal cells. Important in development Electrical synapses
are built for speed Chemical synapse in neuromuscular junction
Synaptic cleft Synaptic cleft Delay in chemical synapse
Delay of about 1 ms Requirements of Chemical Synaptic
Transmission.
Mechanism for synthesizing and packing neurotransmitter into
vesicles. Mechanism for neurotransmitter release Mechanism for
producing an electricalor biochemical responseto neurotransmitter
in postsynaptic neuron. Mechanism for removing transmitter from
synaptic cleft. must be carried out very rapidly. Mechanism for
synthesizing and packing neurotransmitter into vesicles. Criteria
that define a neurotransmitter:
Must be present at presynaptic terminal Must be released by
depolarization, Ca++-dependent Specific receptors must be present
Neurotransmitters may be either small molecules or peptides
Mechanisms and sites of synthesis are different Small molecule
transmitters are synthesized at terminals, packaged into small
clear-core vesicles (often referred to as synaptic vesicles
Peptides, or neuropeptides are synthesized in the endoplasmic
reticulum and transported to the synapse, sometimes they are
processed along the way.Neuropeptides are packaged in large
dense-core vesicles eptide peptide Neurotransmitter Synthesis and
Storage
Synthesis of peptide neurotransmitters Synthesis of amine and amino
acids Mechanism for neurotransmitter release Neurotransmitter
Release
Action potential enters the axon terminal. Voltage gated Ca++
channels open. Ca++ activates proteins in the vesicle and active
zone. Activated proteins causes synaptic vesicles to fuse with
membrane. Neurotransmitter is released via exocytosis. Note:
Peptide release requires high frequency action potentials and is
slower (50 msec vs. 0.2 msec). Active zone With action potential
Without action potential 1 vesicle in sec = quantal release May
produce unit potential in post synaptic 150 vesicle in 1 msec= /sec
at the nerve-muscle synapse Synapsin Rab SNAREPROTEINS V-SNARE VAMP
(synaptobervin)- synaptotagmin T-SNARE SNAP 25 -syntaxin Proteins
have been identified that are thought to
(1) restrain the membrane in response to Ca vesicles so as to
prevent their accidental mobilization (2) target the freed vesicles
to the active zone, (3) dock the targeted vesicles at the active
zone and prime them for fusion, (4) allow fusion and exocytosis (5)
retrieve the fused membrane by endocytosis The importance of the
SNARE proteins in synaptic transmission is emphasized by the
finding that all three proteins are targets of various clostridial
neurotoxins. All of these toxins act by inhibiting synaptic
transmission. Mobilization The vesicles outside the active zone
represent a reserve pool of transmitter. They do not move about
freely in the terminal but rather are restrained or anchored to a
network of cytoskeletal filaments by the synapsins, a family of
four proteins (Ia, Ib, IIa, and IIb) When the nerve terminal is
depolarized and Ca2+phosphorylated by the Ca/calmodulin-dependent
protein kinase. Phosphorylation frees the vesicles from the
cytoskeletal constraint, allowing them to move into the active zone
targeting or trafficking The targeting of synaptic vesicles to
docking sites for release may be carried out by Rab3A and Rab3C,
These Rab proteins bind to synaptic vesicles Hydrolysis of the GTP
bound to Rab, converting it to GDP, may be important for the
efficient targeting of synaptic vesicles to their appropriate sites
of docking. Docking Docked vesicles lie close to plasma membrane
(within 30 nm) According to this theory, specific integral proteins
in the vesicle membrane (vesicle-SNARES, or v-SNARES) bind to
specific receptor proteins in the target membrane (target membrane
or t-SNARE) In the brain two t-SNARES have been identified:
syntaxin, a nerve terminal integral membrane protein, and SNAP-25,
a peripheral membrane protein of 25 kDa mass. In the synaptic
vesicle the integral membrane protein VAMP (or synaptobrevin) has
been identified as the v-SNARE. Priming Primed vesicles can be
induced to fuse with the plasma membrane by sustained
depolarization, high K+, elevated Ca++, hypertonic sucrose
treatment Fusion Vesicles fuse with the plasma membrane to release
transmitter.Physiologically this occurs near calcium channels, but
can be induced experimentally over larger area (see priming).The
active zone is the site of physiological release, and can sometimes
be recognized as an electron-dense structure. . Neurotransmitter
Recovery and Degradation
Neurotransmitters must be cleared from the synapse to permit
another round of synaptic transmission. Methods: Diffusion
Enzymatic degradation in the synapse. Presynaptic reuptake followed
by degradation or recycling. Uptake by glia Uptake by the
postsynaptic neuron and desensitization. Anticholinesterases drugs
as:
myasthenia gravis, a disorder of function at the synapse between
cholinergic motor neurons and skeletal muscle. Dopamine releaseand
reuptake Cocaine inhibits dopamine reuptake
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