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Figure 5.2
The Synapse
A functional connection between surfaces
Signal transmission zone
Synapse synaptic cleft, presynaptic cell, and
postsynaptic cell
Synaptic cleft space in between the presynaptic and
postsynaptic cell
Postsynaptic cell neurons, muscles, and endocrine
glands
Neuromuscular junction synapse between a motor
neuron and a muscle
The Synapse
Axon terminal: found in motor neurons
Axon varicosities: ie swellings. Arranged like beads on a string and
contain neurotransmitter containing vesicles
En passant synapse: CNS. Consists of a swelling along the axon
Spine synapse: presynaptic cell connects with a dendritic spine on
the dendrite of the postsynaptic cell
The Synapse
Axodentritic: between axon terminal of one neuron and the dendrite
of another
Axosomatic: between the axon terminal of one neuron and the cell
body of another
Dendrodendritic: between dendrites of neurons (often are electricla
synapses)
Axoaxonic: between an axon terminal of a presynatpic neuron and
the axon of a postsynaptic neuron.
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Electrotonic
Action potentials
Saltatory conduction
Chemical and electrical synapses
Figure 5.26
Chemical synapse
Fast
Sloooooow
Bi-directional
Unidirectional
Postsynaptic signal is
similar to presynaptic
Excitatory
Excitatory or inhibitory
Electrical synapses
cells connect via gap junctions
- membranes are separated by 2 nm
- gap junctions link the cytosol of two cells
- provide a passageway for movement of very
small molecules and ions between the cells
- gap junction channels have a large conductance
- NO synaptic delay (current spread from cell to cell is instantaneous)
- important in some reflexes
- chemical synapses do have a significant delay ie slow
- commonly found in other cell types as well i.e. glia
- can be modulated by intracellular Ca2+ , pH, membrane voltage,
calmodulin
- clusters of proteins that span the gap such that ions and small
molecules can pass directly from one cell to another
Figure 5.27
Chemical Synapse
most common type of synapse
electrical signal in the presynaptic cell is communicated to the
postsynaptic cell by a chemical (the neurotransmitter)
separation between presynaptic and postsynaptic membranes is
about 20 to 30 nm
a chemical transmitter is released and diffuses to bind to receptors
on postsynaptic side
bind leads (directly or indirectly) to changes in the postsynaptic
membrane potential (usually by opening or closing transmitter
sensitive ion channels)
the response of the neurotransmitter receptor can depolarizes
(excitatory postsynaptic potential; epsp) or hyperpolarizes (inhibitory
postsynaptic potential; ipsp) the post-synaptic cell and changes its
activity
significant delay in signal (1 msec) but far more flexible than
electrical synapse
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Neurotransmitters
Characteristics
Synthesized in neurons
Released at the presynaptic cell following
depolarization
Bind to a postsynaptic receptor and causes an
effect
Neurotransmitters, Cont.
More than 50 known substances
Categories
Amino acids
Neuropeptides
Biogenic amines
Acetylcholine
Miscellaneous ..
Neurotransmitters
Neurotransmitters cont.
Signal Strength
Influenced by neurotransmitter amount and
receptor activity
Neurotransmitter amount: Rate of release
vs. rate of removal
Release: due to frequency of APs
Removal
Passive diffusion out of synapse
Degradation by synaptic enzymes
Uptake by surrounding cells
Graded Potentials
Figure 5.4
Figure 5.6
Metabotropic
Channel changes shape
Signal transmitted via
secondary messenger
Ultimately sends signal to
an ion channel
Slow
Long-term changes
Figure 5.28
Neurotransmitter receptors
Different types of neurotransmitter receptors
Functional Type Ligand Ion Channel
Excitatory Receptors
Acetylcholine
Glutamate Na+/K+; Ca2+
Glutamate
Na+/K+
Serotonin Na+/K+
Inhibitory Receptors
Glycine Cl-
Na+/K+
Cl-
Amount of Neurotransmitter
Influenced by AP frequency which influences
Ca2+ concentration
Control of [Ca2+]
Removal of Neurotransmitter
a)
b)
recycled by uptake
- most neurotransmitters are removed by Na+/neurotransmitter
symporters
- due to a specific neurotransmitter transporter
- recycled by uptake into presynaptic terminal or other cells
(glial cells will take up neurotransmitters)
c)
Neurotransmitters - stages
1.
Synthesis
- all small chemical neurotransmitters are made in the nerve
terminal
- responsible for fast synaptic signalling
- synthetic enzymes + precursors transported into nerve terminal
- subject to feedback inhibition (from recycled neurotransmitters
- can be stimulated to increase activity (via Ca2+ stimulated
phosphorylation)
2.
Presynaptic vesicles
Two groups
i) low molecular weight, non-peptide
e.g. acetylcholine, glycine, glutamate
ii) neuropeptide (over 40 identified so far and counting..)
Presynaptic vesicles
There are 2 types of secretory vesicles
We will only talk about small chemical synaptic vesicles
Neuropeptides are made and packaged in the cell body and
transported to synapse)
Small chemical neurotransmitter vesicles
responsible for fast synaptic signaling
store non-peptide neurotransmitters,
e.g. acetylcholine, glycine, glutamate
enough vesicles in the typical nerve terminal to transmit a few
thousand impulses
exocytosis only occurs after an increase of internal Ca 2+ (due to
depolarization) and at active zones (regions in the presynaptic
membrane adjacent to the cleft)
Presynaptic vesicles
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Vesicle Exocytosis
Vesicle Exocytosis
non-peptide transmitters
SNARE hypothesis
The SNARE Hypothesis for Transport Vesicle Targeting and Fusion
SNARE is an acronym for SNAP receptor (SNAP stands for soluble Nethylmaleimide-sensitive factor attachment proteins).
SNARES are involved in the mediation of protein transport between
various plant organelles by small membrane vesicles.
Two families:
i) V-SNARE - vesicle membrane proteins
ii) T-SNARE - target membrane proteins
SNARE hypothesis
1. Vesicle docking occurs between the VSNARE and T-SNARE proteins
2. The combined proteins act as a receptor for
an ATPase that utilizes ATP to generate the
"docked" form
3. One of the proteins is a Ca2+ sensor such
that when Ca2+ enters the synapse the
vesicle fuses with the plasma membrane and
releases its contents
4. The membrane and proteins are then
recycled through endocytosis (clatharin coat
and dynamin etc.) and reused.
Acetylcholine
Primary neurotransmitter at the vertebrate
neuromuscular junction
Figure 5.17
Synaptic Plasticity
Change in synaptic function in response to patterns of
use
Synaptic facilitation APs neurotransmitter
release
Synaptic depression APs neurotransmitter
release
Post-tetanic potentiation (PTP) after a train of high
frequency APs neurotransmitter release
Figure 5.32
Long-term potentiation
Postsynaptic Cells
Have specific receptors for specific
neurotransmitters
e.g., Nicotinic ACh receptors
Electrotonic
Action potentials
Saltatory conduction
Chemical and electrical synapses
Also:
Shape and speed of action potential
Due to diversity of Na+ and K+ channels
Multiple isoforms
Encoded by many genes
Variants of the same protein
Voltage-gated K+ channels are highly diverse (18 genes
encode for 50 isoforms in mammals)
Na+ channels are less diverse (11 isoforms in mammals)
Table 5.2
Channel Density
Higher density of voltage-gated Na+
channels
Lower threshold
Shorter relative refractory period