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Lecture 2 Synapses
Neuron-cell communication
http://biolpc22.york.ac.uk/632/nervelectures.html
Aim
to know: mechanism of synaptic action drugs which interfere with synaptic action diseases of synapses
Reading Matter Book
Nicholls DG (1994) Proteins Transmitters and Synapses. Blackwell
Papers: Jessell TM, Kandel ER (1993) Synaptic trans-
mission - a bidirectional and self-modifiable form of cell-cell communication Cell 72S 1-30
Whittaker, V. (1990) The contribution of drugs and toxins to understanding of cholinergic function Trends Pharm Science 11: 8-13 (in the photocopy collection)
Revision
Neurons have channels voltage gated ligand gated
Resting and action potentials depend on voltage gated channels
Connections between neurons usually called synapses
Electrical connections Membrane resistance
too high for direct current flow from cell to cell
p o st-syna p ticp re -syna p tic
Na +
gap junction
Chemical connections release chemical transmitter respond with receptors advantages
effective excite or inhibit variable gain
disadvantages slower than electrical [??]
Examples of synaptic connections Examples from snail
neurons Excitation
Inhibition
Schematic diagram
neuromuscular junction
Freeze fracture
resting
stimulated
Quantal release
Miniature EPSP time traces
Stimulated EPSP overlaid traces
EPSP - excitatory post-synaptic potential
Ca++ needed for release Ca++ dye in
presynaptic neuron
[Ca] rises at end of action potential
Ca++ block stops synapse presynaptic Vm
(voltage clamp) presynaptic I Ca++
postsynaptic Vm
Ca++ block stops synapse presynaptic
EGTA blocks transmission
control EGTA
Vesicle fusion cycling
Vesicle cycling? fusion hypothesis kiss & run
clathrin coating
fusion
kiss & run
Synaptic Toxins
tetanus & botulinum toxins blocks transmitter
release interacts with
(vesicle/membrane proteins) produced by Clostridium
bacteria
ACh cycling
ACh pumped into vesicle
ACh esterase
Summary so far
transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by
depolarisation from action potential
Pharmacology of receptors many kinds of receptors
ACh glutamate, glycine serotonin, dopamine peptides, FMRFamide
separate pharmacologically each receptor binds its
own unique profile of drugs
Pharmacology of receptors Nicotinic ACh
receptor agonist - nicotine,
succinylcholine antagonist - curare,
bungarotoxin Muscarinic ACh
receptor agonist - muscarine antagonist - atropine
Ionotropic & Metabotropic Ionotropic
receptor binding opens hole
ions flow through metabotropic
receptor binding activates G-protein
requires second messenger
7 transmembrane format
phosphorylates another protein [channel]
Second messengers
make synapses slow
cAMP IP3/DAG/PKC arachidonic acid
= = norepinephrine
How does 5-HT act?
apply 5-HT to cell
patch elsewhere
Effect of 5-HT
5-HT could block a channel reduce chance of
opening increase chance of
closing reduce current
5-HT = = serotonin
Effect of 5-HT 5-HT closes K+ channels
channel size the same reduced chance of opening
Summary so far
transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by
depolarisation from action potential multiple kinds of receptor
ionotropic / metabotropic different transmitters
Excitation and inhibition
temporal summation
spatial summation
Reversal of IPSPs
Inhibitory post-synaptic potentials reverse at -70 (K+) or -50mV (Cl-)
Pre- & Post- synaptic inhibition Post-synaptic
inhibition leads to summation of excitatory and inhibitory transmitter
Pre-synaptic inhibition occurs between two axons it prevents release
of transmitter
e xc ita tio n
Dia g ra m o f syna p tic re sp o nse
Dia g ra m o f syna p tic la yo ut
p o stsyna p ticinh ib itio n p re syn a p tic
inh ib itio n
Transmitters & disease
myasthenia gravis autoimmune response to ACh receptor
Parkinson’s disease loss of dopaminergic neurons
Confusing points to watch out for Note the difference between
inhibition and antagonism pre- and postsynaptic inhibition conduction and conductance
Summary to end
transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by depolarisation
from action potential multiple kinds of receptor
ionotropic / metabotropic fast/slow
different transmitters excitatory / inhibitory