Transcript Synapse

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‫صدق هللا العظيم‬
‫االسراء اية ‪58‬‬
SYNAPSE
By
Dr. Abdel Aziz M. Hussein
Assist. Prof. of Physiology
Member of American Society of Physiology
Def:
• Functional connection between 2 neurons
• Or Areas of contact between neurons in the C.N.S.
2)Types of Synapses:
A. Chemical
B. Electrical
Most common
Extremely rare
Slow and fatigue
Fast and resist fatigue
One direction only
Occurs in both directions
Physiological anatomy:
Presynaptic
Postsynaptic
Synaptic cleft
small round or oval
knobs→ terminal buttons
or synaptic knobs
Show a thickening directly opposite
the synaptic knob (active zone)
Contains vesicles and
mitochondria
Contains receptors for
neurotransmitters
Types:
Axodendritic
Between axon and
dendrites
Most common and
less excitable
Axosomatic
Between axon and
soma
Axoaxonic
Between axon
and axon
Less common
and most
excitable
•It involves 3 steps:
1) Release of neurotransmitter into
synaptic cleft.
2) Action of the neurotransmitter on
postsynaptic membrane.
3) Termination of synaptic transmission.
•It involves the following steps:
• During rest, both the pre. and postsynaptic
membrane have R.M.P is about -70 mV.
• Stim. of presynaptic neuron → generation of AP
→ AP reaches the synaptic knob→ transient
opening of the VGCa2+ channels  Ca2+ influx
→ Ca2+ causes the vesicles to fuse with the
knob membrane at active zones  vesicles
release the transmitter by exocytosis in cleft
• The number of vesicles ruptured depends upon
the concentration of Ca2+ within the active zone
of the knob.
• The empty vesicles then separated from the
knob membrane and mobilized back and fuse
with the smooth E.R.
• Post-synaptic receptors are 2 types;
Ligand-gated ion
channels
When neurotransmitter
bind to these receptors →
produces structural
changes →↑the channels
permeability to ions
2 types; cation and
anion channels
G-protein coupled
receptors
These receptors bind to
G-protein (attached to
GTP and GDP)
G-protein consists of 3
components; α; β, and γ
Cation Channels
Its
excitatory transmitter
transmitter
Structure
Their inner walls are lined
with -ve charges →allow the
passage of Na, K and Ca
and not allow Cl
Action
When these channels open
Na influx, K efflux occur, but
the total influx of Na is
greater
than
K
efflux
because the driving force for
Na influx is greater than K
efflux (about 7.5 times)
→depolarization
of
the
postsynaptic membrane
Anion Channels
inhibitory transmitter
They have small bore,
so
not
allow
the
passage of Na, K, and
Ca
because
their
hydrated forms have
large sizes
Opening
of
these
channels
as
Cl
channels→ ↑ influx of
Cl
→
causing
hyperpolarization
of
the
membrane→
inhibits
the
postsynaptic neuron.
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Biophysics , Abdelaziz Hussein
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Biophysics , Abdelaziz Hussein
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•Binding of transmitter to its receptor→ G- protein is
activated (by replacement of its GDP with GTP) →
separates the α component from the G-protein.
•The separated active α component can perform;
1. Opening specific ion channels e.g. 2nd- messenger
gated K channels
2. Activation of particular enzymes→ catalyze the
formation of the 2nd messengers, such as cyclic
AMP, cyclic GMP, IP3,diacylglycerol (DAG)
3. Regulation of gene transcription→ control synthesis
and production of certain proteins within the neuron
• Postsynaptic potentials (PSPs) are 2 major types:
1. EPSPs
2. IPSPs
1)Def.
• It is a state of partial depolarization which occurs in
the postsynaptic membrane due to single presynaptic
impulse
2)Mechanism:
• When the excitatory chemical transmitter bind to and
open ligand-gated cation channels→ allow much Na
influx than K efflux→ depolarization of postsynaptic
membrane → brought the postsynaptic membrane
potential close to the threshold for excitation → called
EPSP.
3) Characters or properties :
1. Partial depolarization not reach firing level
2. Increases the excitability as it carries the membrane
potential to FL
3. Localized i.e. not spread.
4. Short duration i.e. decays within 15 m.sec.
5. Its amplitude (very small) about 0.5 mv
• To produce action potential must be summated.
• The summation is of 2 types: spatial and temporal
summation
Summation :
• A depolarization of at least 10 to 20 mV is required to
reach the usual threshold, so EPSPs must be
summated
a) Spatial:
• By stimulation of several presynaptic fibers that
converge on the post synaptic neuron at the same
time.
b) Temporal:
• By stimulation of a single presynaptic neuron
repetitively (successively) within very short duration
(less than 15 m.sec).
•
When the summated EPSPs reach the firing level, This
will generate an action potential at the initial segment of
the axon (axon hillock).
•
During rest: some Ca2+ enters the synaptic knob 
release of few vesicles of neurotransmitter → weak
depolarization of postsynaptic membrane → miniature
EPSP
1)Def.
• It is a state of partial hyperpolarization which occurs in
the postsynaptic membrane due to single presynaptic
impulse
2)Mechanism:
• When the inhibitory chemical transmitter bind to and open
ligand-gated anion channels→ allow much Cl influx →
hyperpolarization of postsynaptic membrane → brought
the postsynaptic membrane potential away from the
threshold for excitation → called IPSP.
3) Characters or properties :
1. Partial hyperpolarization not reach firing level
2. Decreases the excitability as it carries the
membrane potential to FL
3. Localized i.e. not spread.
4. Short duration i.e. decays within 15 m.sec.
5. Its amplitude (very small) about 0.5 mv
• To produce action potential must be summated.
• The summation is of 2 types: spatial and temporal
summation
•
During rest: some Ca2+ enters the synaptic knob 
release of few vesicles of neurotransmitter → weak
hyperpolarization of postsynaptic membrane →
miniature IPSP
•
•
A Postsynaptic neuron may receive many presynaptic
terminals from several hundreds of neurons, some of these
terminals are excitatory and the others are inhibitory.
So, both EPSP & IPSP are produced and the effect on the
postsynaptic membrane depends upon the net ability of
summated postsynaptic potential to drive the membrane either
towards or away from threshold level
• It occurs when the transmitter is removed from
the synaptic cleft by one or more of the following
ways:
i) Active reuptake of the transmitter into the
presynaptic terminal.
ii) Enzymatic degeneration e.g.: hydrolysis or
oxidation….etc.
iii) Diffusion to the interstitial fluid.
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DIFFUSION
AND
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EXCRETIO
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ANS, Abdelaziz Hussein
Neuronal
Uptake
ENZYME
HYDROLYSIS
52
Types : 3 types
Presynaptic
Occurs when
excitatory synapse
is inhibited by
inhibitory
interneuron
Postsynaptic
Occurs when the
pre-synaptic
terminal release an
inhibitory
transmitter
Recurrent
Occurs by
recurrent
inhibitory
interneuron
circuits
C
A
B
Postsynaptic inhibition
Presynaptic inhibition
•Mediated by inhib. interneurons → end on excitatory pre-synaptic
terminals (Axo-axonic Synapses)
•These inhibitory interneurons, thus can modify the rate of release
of neurotransmitter
Presynaptic inhibition
•Mechanism:
•GABA opens the Clchannels in the excitatory
presynatpic terminal 
increase Cl- influx  leading
to decrease in the amplitude
of the action potentials
arriving at the knob 
decrease Ca2+ influx 
decrease the amount of
neurotransmitter released 
decrease in post-synaptic
response ( EPSP)
Presynaptic inhibition
•Significance:
•It occurs in many sensory and motor pathways in
nervous system. It is involved in:
1. Process of lateral inhibition → strongly stimulated
neurons inhibit the less stimulated surrounding
neurons.
2. Pain control system→ plays a role in blocking the
transmission of pain signals at the level of SGR cells.
Lateral Inhibition
Pain Control system
Recurrent inhibition
•Synapse allow conduction of the impulses in one direction
only; from the presynaptic to the postsynaptic neurons →
Bell- Magendie law.
•This is because transmitter is present in the presynaptic
neuron not the postsynaptic neuron
•Def.,
•It is the time that passes between arrival of an action
potential to the synaptic knob and the occurrence of
response in the postsynaptic neuron
Time: 0.5 msec
Cause:
This represents the time required;
1. Release and diffusion of the
neurotransmitter
2. Its binding with its postsynaptic
receptors and generation and
summation of EPSPs.
Signficance: calculate number of synapses in reflex action
•Def.,
•Rapid and intense stimulation of synapse→ progressive
decline in synaptic transmission and the synapse may in
severe conditions, stop functioning
.. . .. ...
. . .Ach . . .
..........
Rate of reuptake
Rate of release
Ca ions
Cause:
•It results mainly from depletion of the neurotransmitter
stores the in the synaptic knobs→ because in intensive
stimulation the resynthesis and reuptake mechanisms
that fill these stores are unable to provide all the
demands for the transmitter
Significance
•Protective mechanism against excessive neuronal
mechanism e.g. in epileptic fit
•Def.,
•Rapid stimulation of presynaptic terminals for a period of
time, the synapse becomes more responsive to subsequent
stimulation than normal for a period of seconds or even
minutes
Cause:
•Due to ↑ of the Ca ions concentration in the synaptic
knob (due to weak Ca pump) → more and more vesicles
to release their transmitter→ greater response of the
postsynaptic neuron
Significance:
•May have a role in the memory processes
•Def.,
•Brief but repetitive, stimulation of presynaptic
terminals results in long-lasting enhancement of
synaptic transmission (lasts for several days).
Cause:
•Caused mainly by an↑ of the intracellular Ca
concentration in the postsynaptic neuron rather
than the presynaptic knob produced by activation
and opening of certain Ca channels in the
postsynaptic membrane
Significance:
•Occurs in many parts of the
CNS
•Has a special significance in
the hippocampus which has
an important role in learning
and memory
-Normal function of the neuron is highly dependent upon
an adequate O2 supply
- Marked hypoxia for a very short period, (a few
seconds), causes loss of excitability of many neurons
and stop of synaptic transmission.
- When the blood supply to the brain is markedly
reduced→ coma occurs within less than 7 seconds.
•Alkalosis→ ↑es excitability of neurons→ at pH 7.8 to 8.0
severe convulsions occurs.
•Acidosis→ ↓es excitability of neurons→ at pH around
7.0 coma occurs.
•This latter condition is always seen in severe uremic or
diabetic acidosis.
i)Caffeine and theophylline→↑ neuronal excitability by
↓ing the threshold for excitation of the postsynaptic
neurons.
ii)Strychnine →↑ neuronal excitability by interfering with
the action of glycine (an inhibitory neurotransmitter) on
the neurons.
iii)Anesthetics and hypnotics →↑ threshold for excitation
of the neurons→↓ synaptic transmission.
•Neurotransmitters of the C.N.S. classified into 2 groups:
1) Small- molecular weight neurotransmitters:
are rapidly acting
2) Large- molecular weight neurotransmitters:
are slowly acting
•They are classified into 4groups:
Class (I): Acetyl choline
Class II): Biogenic Amines e.g.
Noradernaline, adrenaline, Serotonin, Histamine & dopamine
Class (III): Amino acids neurotransmitters e.g. Glutamate
& Asparate (excitatory) GABA & Glycine (inhibitory)
Class (IV): Nitric Oxide (NO)
•They include :
1. Substance-P: neuropeptide for pain transmission.
2. Opioid peptides: e.g.: (Enkephalins & Endorphins).
• Neuropeptides prevent pain transmission.
3. Some neuropeptides coexist with
• Acetyl choline as V.I.P and with
• Noradrenalin as neuropeptide Y (N P Y).
Small M.W. neurotransmitters
Large M.W. neurotransmitters
Rapidly acting
Slowly acting
Most of them are synthesized
and stored at presynaptic
terminals
They are synthesized and
stored in the soma of the
presynaptic neuron and then
transported along axons into
the presynaptic terminals
Synaptic vesicles contain neuropeptides co-exist with synaptic
vesicles containing neurotransmitters and both are released
simultaneously by the action potential that reaches the synaptic
knob.
Important for fast responses
Neuropeptides can prolong the
e.g.:
actions of low M.W.
1. Transmission of sensory
transmitters at the postinformation to C.N.S.
synaptic neurons.
2. Transmission of motor
impulses from C.N.S to ms.
Small MW. Neurotransmitter
Large MW. Neurotransmitter
Small M.W. neurotransmitters
Large M.W. neurotransmitters
Rapidly acting
Slowly acting
Most of them are synthesized
and stored at presynaptic
terminals
They are synthesized and
stored in the soma of the
presynaptic neuron and then
transported along axons into
the presynaptic terminals
Synaptic vesicles contain neuropeptides co-exist with synaptic
vesicles containing neurotransmitters and both are released
simultaneously by the action potential that reaches the synaptic
knob.
Important for fast responses
Neuropeptides can prolong the
e.g.:
actions of low M.W.
1. Transmission of sensory
transmitters at the postinformation to C.N.S.
synaptic neurons.
2. Transmission of motor
impulses from C.N.S to ms.
THANKS