Synapses Neurotransmitter (NT) receptors NT removal
Electrical (rare in CNS) – located at Embedded in postsynaptic density, 2 main types: Mechanisms:
CNS Neurotransmitters
gap junctions (2 connexons)
between very close neurones. Allow
Ligand-gated ion channels
Structure:
- Diffusion (blood)
- Enzymatic
fast, direct, bi-directional transfer. - Membrane-spanning proteins degradation
Chemical – slower, unidirectional (transmembrane) - Re-uptake into
signals using neurotransmitters. - 4-5 subunits = pore the presynaptic
Neurotransmitter = synthesised in - Ion selective (one or more) neurone by
presynaptic neurone, exert action on Activation presynaptic cell
postsynaptic cell, exogenous effect= - Ligand binds to active sites or astrocytes
endogenous effect, specific removal - Conformational change (glial cells in the
mechanism - Pore opens CNS)
Their effects are fast and can be excitatory or Re-uptake by
Neurotransmitters - 3 types
inhibitory (depending on the ion) transmembrane
Amino acids, amines and peptides.
G protein-coupled receptor transporter proteins
Peptides are much larger and not as
Components In presynaptic and
common. Amino acids and amines
- Receptor (transmembrane protein) glial membranes.
are synthesised in the pre-synaptic
- G-protein (intracellular) Uses a support
terminal, peptides are synthesised in
- Effector (ion channel or enzyme) mechanism (with
ER and Golgi. But all stored in pre-
Activation: proton anti-porters
synaptic terminal.
- Ligand binds to active sites – a co-transporter-
Cells can release 1 or several
- Conformational change of G-protein with Na+) to Recycle
neurotransmitters.
- Activation of effector (ion NT into synaptic
Depolarisation -> Ca2+ channels
entrance/intracellular cascade of reactions) vesicles
open & influx -> synaptic vesicles
Their effects are slow and longer-lasting.
move to active zone -> exocytosis (+
endocytosis to maintain cell size).
Vesicles are reloaded using
neurotransmitter antiporters.
Neuropeptides Neurotransmitters
Neuropeptides may also be co- Larger Smaller
released with smaller Made in cell body (ER and Golgi body) Made in pre-synaptic terminal
neurotransmitters from the same Stored in dense-core vesicles (from Golgi) Stored in synaptic vesicles
cell. Exocytosis not limited to active zone as it Exocytosis limited to active zone
requires non-localised increase of Ca2+
Neuromodulators
Slower mechanism of action Faster release
Characteristics:
- They are mediators – modulate Autoreceptors (neuromodulator is a normal neurotransmitter)
the transmission of information Found in the pre-synaptic membrane
- Produced by neuronal or non- Sensitive to own neurotransmitter (presynaptic membrane has
neuronal cells (astrocytes) receptors for it)
- May not be stored and released Normally G protein-coupled receptors (some ionotropic)
as conventional Have a self-regulatory mechanism:
neurotransmitters When the concentration of neurotransmitter is too high in the cleft, there
- Regulate pre-synaptic is an inhibition of neurotransmitter release or synthesis (as the
neurotransmitter release or neurotransmitter will act on the pre-synaptic membrane receptors).
post-synaptic excitability Autoreceptors are a part of the normal synaptic communication
- Mainly operate through G
protein-coupled receptors Endocannabinoid system (lipid mediator)
- Produce slower responses feedback system to regulate conventional synaptic transmission
Types: Endocannabinoids are synthesised by the post-synaptic cell when it is
- Conventional neurotransmitters very active
acting on autoreceptors They reduce the opening of pre-synaptic calcium channels, inhibiting
- Lipid mediators e.g. neurotransmitter release
endocannabinoids There are two main G protein-coupled receptors used: CB1 and CB2
- Gaseous mediators e.g. nitric And 2 main ligands (lipids) used: Anandamide (AEA), and 2-Arachydonil
oxide glycerol (2-AG)
Electrical (rare in CNS) – located at Embedded in postsynaptic density, 2 main types: Mechanisms:
CNS Neurotransmitters
gap junctions (2 connexons)
between very close neurones. Allow
Ligand-gated ion channels
Structure:
- Diffusion (blood)
- Enzymatic
fast, direct, bi-directional transfer. - Membrane-spanning proteins degradation
Chemical – slower, unidirectional (transmembrane) - Re-uptake into
signals using neurotransmitters. - 4-5 subunits = pore the presynaptic
Neurotransmitter = synthesised in - Ion selective (one or more) neurone by
presynaptic neurone, exert action on Activation presynaptic cell
postsynaptic cell, exogenous effect= - Ligand binds to active sites or astrocytes
endogenous effect, specific removal - Conformational change (glial cells in the
mechanism - Pore opens CNS)
Their effects are fast and can be excitatory or Re-uptake by
Neurotransmitters - 3 types
inhibitory (depending on the ion) transmembrane
Amino acids, amines and peptides.
G protein-coupled receptor transporter proteins
Peptides are much larger and not as
Components In presynaptic and
common. Amino acids and amines
- Receptor (transmembrane protein) glial membranes.
are synthesised in the pre-synaptic
- G-protein (intracellular) Uses a support
terminal, peptides are synthesised in
- Effector (ion channel or enzyme) mechanism (with
ER and Golgi. But all stored in pre-
Activation: proton anti-porters
synaptic terminal.
- Ligand binds to active sites – a co-transporter-
Cells can release 1 or several
- Conformational change of G-protein with Na+) to Recycle
neurotransmitters.
- Activation of effector (ion NT into synaptic
Depolarisation -> Ca2+ channels
entrance/intracellular cascade of reactions) vesicles
open & influx -> synaptic vesicles
Their effects are slow and longer-lasting.
move to active zone -> exocytosis (+
endocytosis to maintain cell size).
Vesicles are reloaded using
neurotransmitter antiporters.
Neuropeptides Neurotransmitters
Neuropeptides may also be co- Larger Smaller
released with smaller Made in cell body (ER and Golgi body) Made in pre-synaptic terminal
neurotransmitters from the same Stored in dense-core vesicles (from Golgi) Stored in synaptic vesicles
cell. Exocytosis not limited to active zone as it Exocytosis limited to active zone
requires non-localised increase of Ca2+
Neuromodulators
Slower mechanism of action Faster release
Characteristics:
- They are mediators – modulate Autoreceptors (neuromodulator is a normal neurotransmitter)
the transmission of information Found in the pre-synaptic membrane
- Produced by neuronal or non- Sensitive to own neurotransmitter (presynaptic membrane has
neuronal cells (astrocytes) receptors for it)
- May not be stored and released Normally G protein-coupled receptors (some ionotropic)
as conventional Have a self-regulatory mechanism:
neurotransmitters When the concentration of neurotransmitter is too high in the cleft, there
- Regulate pre-synaptic is an inhibition of neurotransmitter release or synthesis (as the
neurotransmitter release or neurotransmitter will act on the pre-synaptic membrane receptors).
post-synaptic excitability Autoreceptors are a part of the normal synaptic communication
- Mainly operate through G
protein-coupled receptors Endocannabinoid system (lipid mediator)
- Produce slower responses feedback system to regulate conventional synaptic transmission
Types: Endocannabinoids are synthesised by the post-synaptic cell when it is
- Conventional neurotransmitters very active
acting on autoreceptors They reduce the opening of pre-synaptic calcium channels, inhibiting
- Lipid mediators e.g. neurotransmitter release
endocannabinoids There are two main G protein-coupled receptors used: CB1 and CB2
- Gaseous mediators e.g. nitric And 2 main ligands (lipids) used: Anandamide (AEA), and 2-Arachydonil
oxide glycerol (2-AG)
