Download Nerve and muscle signalling

Sci2 Lect 5 Synaptic Transmission
©Dr Bill Phillips 2002, Dept of Physiology
•
•
•
•
•
•
Fast Excitatory Postsynaptic Potentials
Ligand gated ion channels
Presynaptic neurotransmitter release
Fast inhibitory synapses
Local circuit currents- synaptic integration
Slow synaptic transmission
Fast and slow chemical synaptic
transmission
• FAST SYNAPTIC
TRANSMISSION
• Transmitter binds to
and opens ligandgated ion channels
• Response takes no
more than a few
milliseconds
• SLOW SYNAPTIC
TRANSMISSION
• Transmitter binds
receptor that activates
second messenger
signalling in
postsynaptic cell
• Response takes
seconds or minutes
Fast Excitatory Postsynaptic Potentials
Excitatory
synapse
Excitatory
synapse
Steps in fast chemical transmission:
• Nerve AP depolarises nerve terminal
• Voltage-gated Ca2+ channels in terminal open
leading to [Ca2+]i
• [Ca2+]i triggers release of transmitter into the
synaptic cleft
• Transmitter activates postsynaptic ligand-gated ion
channels, opening them
• Altered membrane current depolarises or
hyperpolarises postsynaptic cell
Ligand-gated cation channels like the nicotinic
acetylcholine receptor (AChR) are permeable
to both Na+ and K+.
?
Why does opening of these cation channels
result in depolarisation of the postsynaptic
membrane?
+30mV
0 mV
-6 0 mV
Stimulate
Miniature (quantal) responses
• Electrical recordings from postsynaptic
cells reveal Excitatory PostSynaptic
Potentials (EPSPs) when follow transmitter
release from presynaptic nerve terminals
• EPSPs seem to be made up of the
Summation of small (~0.5mV) Miniature
EPSPs sometimes referred to as quanta
Vesicle/quanta hypothesis
• Most neuroscientist think transmitter chemicals
are released in discrete packets or quanta
• The vesicle hypothesis says that these quanta are
contained in synaptic vesicles that are released by
a form of exocytosis
• The ~uniform size of the synaptic vesicles may
explain the fairly uniform quantal amplitude of the
postsynaptic response.
Presynaptic neurotransmitter release: eg
glutamate from excitatory nerve terminals
Presynaptic nerve terminal
voltage -gated
Ca++ channels
ACh
Glut
Glut
ACh
ACh
Glut
ACh
Glut
Glut
ACh
synaptic cleft
AChE
Postsynaptic
infoldings (where
ACh is degraded)
Glutamate
receptors
AChRs
Postsynaptic muscle cell
Role of Ca2+ in transmitter release
• Amplitude of EPSP depends on [Ca2+]o
• [Ca2+]o normally ~1mM if lowered to
0.5mM, number of quanta released drops
greatly, suggesting that the mechanism of
neurotransmitter release is dependent upon
the concentration of Ca2+ inside the terminal
following the action potential.
• SELF TEST- WHY?
Fast inhibitory synapses*
• Major inhibitory
neurotransmitters:
Gamma amino butyric
acid (GABA), glycine
Mot or neurone
Nucleus
Presynaptic
Depolarisation
Postsynaptic
Hyperpolarisation
*Often found on neuron soma
And proximal dendrites
• Ligand-gated Clchannels (eg GABAA
receptor)
How do fast inhibitory synapses
work?
• GABAA receptors and glycine receptors are
Ligand-gated channels selective for Cl• [Cl-]o >>[Cl-] i concentration gradient into cell
• Opening of these channels  inward current of
Cl- equivalent to an  outward current of +ve ions
• Hyperpolarise soma, or short-circuit depolarising
local circuit currents coming from excitatory
synapses
Local circuit currents- synaptic
integration
Muscle fibre
Mot or neurone
Nucleus
Summation of postsynaptic currents
• Excitatory Postsynaptic Currents (EPSCs) spread
through dendrites to cell body (soma)
• Local circuit currents diminish with distance due
to resistance of cytoplasm and leakage channels in
dendrite membrane
• EPSCs from many synapses on different branches
of the dendritic ‘tree’ sum together at the axon
hillock where a ‘decision’ is made whether an
action potential/s is triggered
Synaptic integration
• Plasma membrane stores electrical charge this
means brief opening of channels results in much
longer slower changes in Vm (capacitance
properties)
• Summation of EPSCs occuring within a few
milliseconds of each other sum to raise Vm
• When Inhibitory Postsynaptic Currents (IPSCs)
occur at the same time as EPSCs they help to
lower the Vm and reduce the chance that action
potential/s will be triggered at the axon hillock
Fast and slow chemical synaptic
transmission
• FAST SYNAPTIC
TRANSMISSION
• Transmitter binds to
and opens ligandgated ion channels
• Response takes no
more than a few
milliseconds
• SLOW SYNAPTIC
TRANSMISSION
• Transmitter binds
receptor that activates
second messenger
signalling in
postsynaptic cell
• Response takes
seconds or minutes
Slow synaptic transmission
• Produce delayed changes in postsynaptic current
or other changes in postsynaptic cell
• Seconds or minutes to take effect
• Many types: can involve familiar transmitters (eg
glutamate, GABA) or different ones (eg
dopamine, noradrenaline)
• Different types of receptors- often G-proteincoupled receptors that work through second
messenger systems
Slow synaptic transmission: Effects
Depending on transmitter, receptor and
second messenger system involved may:
• Depolarise postsynaptic cell
• Hyperpolarise
• Reduce or increase membrane
resistance
• Modify gene expression
• Modify transmitter release