Lecture 8 – SYNAPTIC TRANSMISSION Flashcards
Information processing in the nervous system:
- Synaptic transmission
- Electrical synapses
- Chemical synapses
- Neurotransmitter release
- Vesicle and transmitter recycling
The problem:
Transmission of an electrical signal across high resistance membranes and intercellular gaps
- Spark or soup
- Neurons are individual cells
- Unsure whether an electrical continuity or chemical
- Found out later that it was both
Some Terminology:
- Transmitting neuron is the presynaptic neuron
- Receiving neuron is the postsynaptic neuron
- Cells can be both pre- and post-synaptic
- Some cells can make synapses with themselves
- Postsynaptic potential – if it’s going upwards and depolarising its epsp (excitatory) and if it’s going downwards then it is hyperpolarising and is ipsp (inhibitory)
- Direction of transmission if chemical is only one way
Electrical synapses – ‘spark’:
- Gap junction (cardiac cells)
- Allows cytoplasmic continuity of neurons
- Direct transfer of ions and small molecules between cells
- Bidirectional – current can pass in both directions, small holes between the two cells
- In the graphs shown the travel seems to be attenuated which shows a 100mv change in amplitude for presynaptic but only a 1mv change in post synaptic
- Holes act as filter so each individual gap junction only passes a small amount (0.1%)
- Fast transmission – no synaptic delay
Found in all multicellular animals
channels and pores
- Gap junctions allow direct cytoplasmic communication between cells
- Presynaptic cell at top and post at bottom
- Made up of many gap junction ‘channels’/pores – found in plaque at synapse
- Each channel is made up of two connexions (makes a gap junction) and each connexion unit is made up of six connexion subunits
- Pore is around 1-2nm and made up of the 6 connexion subunits – signalling, cAMP etc. can pass
insects
In insects, you have connexions but in human cells there are paniexions which have the same structure but form different proteins (different sequences so no relation).
Properties of Electrical Synapses:
Fast and reliable but are capable of only limited plasticity which means change (contrast chemical synapses – electrical allows for a lack of variation but with chemical we can learn how things work)
- may be two-way (non-rectifying)
- very fast
- often give one-to-one transmission normally attenuated
- allow exchange of other chemicals – small holes
- are used by invertebrates, lower vertebrates and mammals
- are much less common than chemical synapses
¥ Used in fast pathways e.g. escape/defence
¥ Used to promote synchronous activity within a network (groups of neurons) and have been exploited for anti-seizure drugs
Chemical Synaptic Transmission – ‘soup’:
¥ First demonstrated by Otto Loewi at frog heart neuromuscular junction
¥ Acetylcholine released from vagus nerve onto muscle to slow heart rate as it diffuses across the synaptic cleft to the post-synaptic membrane
¥ Synaptic delay = 0.5-2.0 milliseconds
neurotransmitters in the heart
- 200 known neurotransmitters (GABA Ach)
- used as a model on frog hearts
- if u take a frog heart out and put it in saline the heart keeps beating for an hour more
- if you leave the nerves hanging off you can stimulate the nerves to beat the heart
- when testing this, you can stimulate a particular nerve and the heart will begin to slow down
- it is now known that Ach stimulated the decreased heart rate
- when doing this to a heart that did not have a vagal nerve attached there was the exact same effect
- low resistance of the synaptic cleft causes it to leak out, hence it released something into the saline solution
- when the solution is pumped into another chamber with another heart, the neurotransmitter can bind onto the second receptors on the heart and the heart rate will slow down for that too
- using a different nerve can cause the heart rate to speed up
- if gap junctions were present then you would not be able to stimulate a response in the second heart
chemical synapse
- influx of Ca2+ occurs very close to the area where the vesicles are docked to the membrane
- local increase in Ca2+ so if measured anywhere else in the cell the concentration would be quite low
- diffuses 20nm and binds to receptors causing a change in the psp
this process is quite slow around 35ms
- active zone is the fusion sites
Vesicular release/ fusion:
- Docking – proteins keep the vesicles close to but not attached to the plasma membrane
- Ca2+ entry – due to action potential, calcium increases in the local area and causes a change in the proteins which causes vesicle fusion
Fusion – vesicle opens, transmitter is released and will pass through the low resistance pathway which is wasteful and only a small percentage finds its receptor
4. Recycling – if there was no recycling the synapse would constantly keep growing and you would run out of neurotransmitter and vesicles
SNARE Hypothesis:
- V-SNAREs (vesicle) = synaptobrevin, synaptotagmin (green and anchored inside the vesicle)
- t-SNAREs (target membrane) = syntaxin, SNAP-25 THE MAJOR CALCIUM BINDING COMPLEX CAUSING CONNECTIONS TO TWIST EVEN TIGHTER FOR THE MEMBRANE TO FUSE WHICH REQUIRES A LOT OF ENERGY (red – transmembrane regions to anchor them and cytoplasmic regions to zipper them together)
Ca2+ triggers neurotransmitter release:
docking sites include the SNARE proteins
- transferred information
Spontaneous neurotransmitter release persists in the absence of Ca2+:
Release is quantal – a fixed amount
vesicle release is a probability event
- the vesicle release is increased by the release of calcium (CALCIUM IS NOT A TRIGGER)
- the absence of calcium still sees vesicles being released but just at a very low percentage
- this is because of spontaneous release – single vesicles released (1 a second) PSPs 3mv in magnitude and will release the same amount each time
- evoked release is when an action potential fires (30-200 a second is released – the usual quantal content)
spontaneous is ‘minis’ and evoked is the action
Miniature postsynaptic potentials (‘minis’):
¥ occur spontaneously, even in zero extracellular Ca2+
¥ have amplitudes that are multiples of a quantal unit
¥ are due to release of one or a few quanta (= vesicle)
- As extracellular Ca2+ is lowered, epsp amplitude decreases in a step-wise manner
- Quantal analysis of AP-evoked epsps shows that they involve release of up to 200 quanta per AP. ‘Quantal Content’ = no of quanta released for one AP
- Each quantum (packet/vesicle) contains several thousand molecules of ACh
