Lecture 9 Flashcards
What is the synapse?
A specialized gap region between two apposing cell membranes across which signals (electrical and chemical) can pass
What does “apposing” mean?
Two structures that are in close proximity to one another
What is synaptic transmission?
Process underlying the cell-cell transfer of electrical ligands
What has the frog heart experiment demonstrated?
The existence of chemical synapses e.g. ACh
What are the common features of chemical synapses?
Presynaptic cell, postsynaptic cell, synaptic cleft, secretory granules, synaptic vesicles
What does the presynaptic cell do?
Many mitochondria to produce energy to clear Ca from terminal (active zone: where vesicles are released)
What does the postsynaptic cell do?
Postsynaptic density: where receptors are found
How wide is the synaptic cleft?
20 - 50 nm wide: 10 times the width of the separation at gap junction
What is the synaptic cleft?
Matrix of fibrous extracellular protein (extracellular proteins enable the active zone and postsynaptic density to carry out their fortune
What do secretory granules contain?
Peptide neurotransmitter
What do synaptic vesicles contain?
Non-peptide neurotransmitters
What are the two types of chemical synapses?
Neuron to non-neuronal cell, neuron to neuron
What are features of neuron to non-neuronal cell chemical synapses?
Most common: motor neuron to skeletal muscle, the neuromuscular junctions
Autonomic neurons to glands, smooth muscle and heart
Where are neuron to neuron chemical synapses found?
Within the CNS: found between pre and postganglionic neurons in ANS as well
What are features of neuron to neuron chemical synapses?
Extremely varied, different neurotransmitters, different sizes and morphologies
Why do we need synapses?
Simple transference of a signal
Synapses allow information processing that is: complex. subtle and flexible
How can divergence of output be activated?
synapses
What can defective neurotransmission lead to?
many neurological and psychiatric disorders
What causes Parkinson’s disease and what happens?
Lose neurons and synapses in a certain area, lose coordination
What does the neuromuscular junction provide?
Fast and reliable neurotransmission
Motor neuron action potentials always cause muscle cell action potentials
Uses ACh
One of the largest synapses in the body: generally larger than CNS neuron
What is a specialization of presynaptic membrane?
Large number of active zones
What is a specialization of postsynaptic membrane?
Contains junctional folds, densely filled with neurotransmitter receptors
Junctional folds: put more receptors in a certain area
- neurotransmitters can bounce around more before it is degraded
- neuromuscular junction specific
How many neurons are there in the human brain?
86 billion
What are the four different synaptic arrangements within the CNS?
Axodendritic
Axosomatic
Axoaxonic
Dendrodendritic
What can axoaxonic synapses do?
Can control the signal from the axon from the other neuron
e.g. Inhibitory or excitatory axon - prevents action potential from reaching presynaptic terminal
What is a consequence of synapses having different sizes, grow and shrink?
Lots of plasticity
Transmission between neurons can get better or worse
Pathway in brain can get fixed in a certain way
Always occurring (memory)
Can synapses release transmitters from more than one active zone in a terminal?
yes
Can larger synapse have more active zones than smaller ones?
yes
Give examples of how synapse arrangement and structure relate to their function:
Engulfing type: good for reflexes
Reliable neurotransmission
Localize straight away
What is used for further classification of pre and postsynaptic cells?
Appearance:
Assymetrical membrane differentiations - presynaptic membrane is thinner than postsynaptic membranes
Usuallly excitatory
Symmetrical membrane differentiations - densities are of equal thickness
Usually inhibitory
What are the seven principles of chemical synaptic transmission?
- Neurotransmitter molecules are synthesized and packaged in vesicles
- An action potential arrives at the presynaptic terminal
- Voltage-gated Ca channels open. Ca enters.
Ca channels are normally closed at negative potentials
Opens at -40mV and all are open at -10mV
Ca moves down electrochemical gradient - A rise in Ca triggers fusion of synaptic vesicles with the presynaptic membrane
- Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell
Neurotransmitter bounces around towards area with few neurotransmitters
Might get taken up or get degraded by an enzyme or diffuse across and hit a receptor
Might hit another receptor or be released to be degraded - Bound receptors activate the postsynaptic cell
- A neurotransmitter breaks down, is taken up by the presynaptic terminal or other cells, or diffuses away from the synapse
Depends on amount of receptors and amount of neurotransmitter and size of gap
The bigger the gap the more likely neurotransmitter binds to receptor
What are the three types of neurotransmitters?
Amino acids, amines, peptides
What are examples of amino acid neurotransmitters?
Glutamate (excitatory), GABA (inhibitory), Glycine (inhibitory)
What are examples of amine neurotransmitters?
ACh, noradrenaline, adrenaline, serotonin
What is an example of peptide neurotransmitters?
substance P
What kind of synapse are amino acid and amine neurotransmitter carried in?
Synaptic vesicles (40-50nm diameter)
What kind of synapse are peptide neurotransmitter carried in?
Dense-core secretory vesicles (100-200nm diameter)
Where are synaptic vesicles synthesized in?
Soma
Where are synaptic vesicles filled at?
Presynaptic terminal
What is required for neurotransmitters to be loaded into vesicles?
ATP
Where are dense-core secretory granules synthesized in?
ER; often as precursors
Where do dense-core secretory granules bud from?
Golgi apparatus in soma
Where are dense-core secretory granules transported along?
Microtubules
What amino acid neurotransmitters are abundant in all cells and are used as building blocks of proteins?
Glutamate and glycine
What do neurons need to synthesize GABA and amine neurotransmitters from various metabolic precursors?
Special enzymes: found in presynaptic terminals to allow rapid and local neurotransmitter synthesis. Specialized transporters take the neurotransmitters up into synaptic vesicles
What is docking?
Neurotransmitter release: some vesicles are already docked at active zones within the presynaptic neuronal membrane (Held by SNARE proteins)
Doesn’t touch but is close to active zones
What triggers neurotransmitter release?
Arrival of action potential opens voltage-gated Ca channels
Ca moves into the presynaptic terminal as Eca is 123mV
Triggers vesicle fusion and release (exocytosis)
What are SNARE proteins used in?
exocytosis
Where are SNARE proteins located in?
Presynaptic membrane or vesicles
What do SNARE proteins bind to and why?
Ca - cause vesicle fusion (causes changes in configuration of vesicles)
What is an example of a toxin that selectively destroys SNARE proteins?
Botulinum toxin: from the black widow spider containing an enzyme - blocks synaptic neurotransmission, synappses between nerves and muscles are disrupted
What are the two main types of receptors?
Ligand-gated ion channels (ionotropic)
G-protein coupled receptors (metabotropic)
What are the three main ways to clear neurotransmitters from the synaptic cleft?
- Simple diffusion out of the synaptic cleft
- Reuptake into the presynaptic membrane (or glia) by specific transporters, for recycling
- Enzymatic destruction within the synaptic cleft e.g. AChE
Clearing may be before or after neurotransmitter has activated a receptor
Must be cleared because there will be signal loss in terms of timing if not
What is used to measure how many vesicles have been released?
Capacitance measurement
What is quantal release?
Each synaptic vesicle contains 35-50nM and can cause a mini response at the postsynaptic cell
The effect of one vesicle being released is known as quantal size
Quantal content is the number of quanta (for vesicles) released
What is an inhibitory neurotransmitter for nicotinic ACh receptors?
Curare
What is an inhibitory neurotransmitter for muscarinic ACh receptors?
Atropine
What are ligand gated ion channels permeable to and why?
Na
Skeletal muscle contraction
What do GPCRs activate and why?
K channel
Slows heart down
What do transmitter release at a “fast” excitatory chemical synapse generate?
EPSP
Synaptic transmission is slower and more complex which type of receptor, GPCRs or ionotropic receptors?
GPCR
