Synaptic Transmission

Dr. T Jay-du Preez

Synaptic transmission
Synaptic transmission
 Impulse transmission in the nervous
system:
 Transmission of impulses in humans:
mainly chemical.
 Gap junctions with electrically mediated
transfer does occur.
 Synaptic transmission: takes place in one
direction: presynaptic to postsynaptic
neurons.
Synaptic transmission
Synaptic transmission
 Impulse arrives at presynaptic nerve
terminal
 Transmitter substance is released
 This substance reacts with a postsynaptic
chemical receptor in the subsynaptic
membrane.
 This affects the chemical dependent ion
channels (receptor or ligand) and the
membrane potential of the postsynaptic
cell changes.
Synaptic transmission
Synaptic transmission
 It can also initiate a specific metabolic
response via a second messenger which
underlie plasticity and learning.(e.g. cAMP
in the heart and IP3 in the brain).
Synaptic transmission
 EPSP Excitatory Postsynaptic Potential:
 Develops when transmitter alters
permeability in such a way that membrane
is hypopolarised e.g. when permeability
for Na+ increase.
 Hypopolarisation or EPSP reaches
threshold: impulse generated initial
segment of axon.
 Na+ and K+ channel density very high in
this area.
Synaptic transmission
 Impulse then propagated all along axon.
 EPSP is not an all or nothing response.
 Receptor potential is also not all or
nothing.
 It spreads all over neuron membrane and
lasts 15-20ms.
 EPSP due to discharge from one synaptic
knob not usually enough to exceed
threshold for impulse generation.
Synaptic transmission
 Usually many synapses on each neuron
 EPSP’s produced at several synapses on the same
neuron summate
 Summation=spatial or temporal.
 Spatial: Impulses arrive at several knobs at the
same time.
 Temporal: Impulses arrive repeatedly at the
same synaptic knob before the previous EPSP’s
have subsided.
 Facilitation: Discharge by one synaptic knob is
said to facilitate the effect of another.
Synaptic transmission
 Excitatory transmitter substances
 Acetylcholine Ach
 Noradrenaline NA
 Enzymes present at synapses inactivate
the transmitters after release to stop
effect at postsynaptic membrane.
Synaptic transmission
 Ach inactivated by acetylcholine esterase
 NA inactivated by monoamine-oxidase
(MAO)
 NA also inactivated by catechol-O-
methyltransferase (COMT).
Synaptic transmission
 Transmitter substances disposed by
 1) Re-uptake by presynaptic terminals
 2)Uptake by glial cells
 3)Removal by circulation-broken down by
liver.
Synaptic transmission
 Noradrenaline
 Formed from amino acid phenylalanine or
tyrosine.
 MAO present in nerve endings and COMT
present in many tissues e.g. liver break it
down.
 Excitatory.
Synaptic transmission
 Acetylcholine
 Synthesis in nerve endings from choline
and acetyl-CoA.
 Choline+Acetyl-CoA-----Ach

CAT
(cholineactyltransferase)
 CAT is enzyme catalyzing reaction.
Synaptic transmission
After release Ach is rapidly hydrolysed by
enzyme acetylcholinesterase (ACE) and
the products are taken up by presynaptic
nerve endings.
 Ach---------choline and acetate

ACE
Synaptic transmission
 Ach present throughout CNS
 Works on muscarinic and nicotinic
receptors
 Also in peripheral nervous system in motor
endplates working on nicotinic receptors.
Synapse transmission
 IPSP Inhibitory postsynaptic potential:
 When transmitter alters permeability of
postsynaptic membrane in such a way that
the membrane becomes hyperpolarised.
 May for instance increase permeability for
K+. K+ efflux increases, and membrane
more positive outside than at rest.
 Membrane now less excitable than at rest.
 This is postsynaptic or direct inhibition.
Synapse transmission
 Indirect inhibition also takes place: due to
any condition that prevents discharge of
any neuron in the chain. (e.g. if the
neuron is refractory)
 Presynaptic inhibition is also indirect
inhibition: Neurotransmitter release by
presynaptic ending is reduced/prevented.
Synaptic transmission
 Inhibitory neurotransitters:
 Gamma-aminobutyric acid GABA
 Glycine
Synaptic transmission
 Gamma-aminobutyric acid GABA
 Formed by decarboxylation of Glutamate
 Glutamate decarboxylase catalyses reaction
 Glutamate----GABA

GAD
B6 is a cofactor for GAD
GABA-transaminase catalyzes metabolism of
GABA
Most common inhibitory neurotransmitter in CNS.
Benzodiazepines facilitate GABA effects.
Synaptic transmission
 Glycine:
 Brain stem and spinal cord
 Inhibitory neurotransmitter
 Increases membrane permeability for Cl-
 Binds to NMDA receptors.
Synaptic transmission
 Dendrites increase surface area in CNS for
synapses.
 Action potentials do not develop, only
excitatory/inhibitory potentials-conducted
electronically towards soma/cell body.
 Large part lost before it reaches soma
 Can still contribute to existing EPSP and
IPSP thus increasing or decreasing
potentials.
Synaptic transmission
 Influences:
 Very dependent continuous O2 supply.
 Sensitive to pH:
 Acidosis depresses neural activity
 Alkalosis increases neural excitability.
Synaptic transmission
 Volume transmission:
 Extrasynaptic mechanism of transmission
 Diffusion of chemical substances or
neurotransmitters through extracellular
fluid.
 Neurotransmitters released by neurons
into extracellular fluid.
 Diffuse through fluid and react with
extrasynaptic receptors on distant
neurons.
Synaptic transmission
 Specificity of information transmission depends
upon release of particular neurotransmitter and
location of neurons with specific receptors.
 Volume transmission: mechanism for sustained
mass activation of large numbers of neurons.
 Responsible for “brain tone” and helps with sleep,
vigilance, attention, emotion, mood.
 Primary mechanism for effects of most
pharmacological substance on CNS.
Synaptic transmission
 Impulse transmission to muscle fibres:
 Nervous stimulation needed for
 1) Excitation skeletal muscle
 2)Multi-unit type smooth muscle fibres.
 Pacemaker cells supply heart and visceral
smooth muscle. (rhythmically and
automatically activated)
 These organs however have nerves that
modulate their activity.
Synaptic transmission
Synaptic transmission
 Skeletal muscle:
 Supplied by somatic nervous system.
 Neuromuscular junctions.
 Each muscle fibre supplied by only one nerve
terminal and has a single motor endplate.
 Axons of motor neurons branch extensively.
Each branch supply one fibre.
 Thus when a single motor neuron activated all
the muscle fibres are activated simultaneously.
Synaptic transmission
 Single motor neuron with all the muscle
fibres innervated by is=motor unit.
 Nr. Fibres in a motor unit varies: Fine
precise movement e.g. hand and eyes:
only 3-6 fibresl
 Back muscles contain>1000 fibres/unit.
Synaptic transmission
 Impulse arrives at motor endplate
 Ach released (only transmitter releases by
motor endplate).
 Binds to Ach receptors in subsynaptic
membrane.
 Ach receptors are usually ligand gated
Na+ channels.
 Channels open when Ach binds to them.
 Increased permeability for Na+
Synaptic transmission
 Subsynaptic membrane becomes
hypopolarised
 Called Enplate Potential: Analogous to EPSP.
 When EPP reaches threshold action pot
generated in adjacent membrane and
conducted all along muscle fibre.
 Depolarisation causes contraction of muscle
fibre.
 This is known as excitation-contraction
coupling.
Synaptic transmission
 Ach receptors in endplate also called
nicotinic receptors as they can bind
nicotine.
 Curare poison and cobra snake venom
block impulse transmission: blocks Ach
receptors and block their binding to Ach.
 Paralysis follows.
 Also used in muscle relaxants during
anaesthesia.
Synaptic transmission
Synaptic transmission
 Smooth muscle:
 Supplied by autonomic nervous system
 Nerve terminals not specialized structures.
 Fibres receive two types nerve fibres
which release Ach and NA respectively.
 The heart:
 Supplied by autonomic nervous system
 Modifies cardiac activity
 Substances Ach and NA
Synaptic transmission
 Ion channels may be classified by the
nature of their gating, the species of ions
passing through those gates, and the
number of gates (pores).
 By gating: Voltage gated
 Ligand gated e.g. Ach nicotinic receptors.
 Other gating e.g. second messengers
 By ions e.g. K+ channels, Na+ channels
 Other classifications e.g. two pore
channels