Neurotransmitters Flashcards
What is synaptic transmission?
How fast are they?
Release process - Information transfer across the synapse requires the release of neurotransmitters and their interaction with the post-synaptic neuron
Very rapid time scale
What are 5 key features of synaptic transmission?
Which of these features give rise to the learning process?
- Rapid timescale
- Diversity
- Adaptability
- Plasticity - synaptic transmission can change any time
- Learning and memory
Adaptibility and plasticity give rise to the learning and memory process eps. the hippocampus
What is the structure of the neuron?
Why do dendrites have spikes called spines?
What is ‘integration of information’?
Each has a:
Soma = cell body, dendrites on the cell body to receive chemical information from other neurons, and an axon to carry the information down
Increase surface area
Collating all the information received by the dendrites, excitatory and inhibitory, to form an overall action (like summation)
Does one neuron only connect to one other neuron / post synaptic knob?
No, one synapse can connect to many - receive many neurotransmitters, which contributes to diversity of their functions
Allows for all that information to be integrated to perform an overall functionn
What are the 3 stages of Synaptic transmission?
- Biosynthesis, packaging, and release of neurotransmitters
- Receptor action
- Inactivation of the neurotransmitters - system will shut down if this fails to occur
About the NTs - give examples of the 3 different ypes of NTs
How is diversity achieved in the synapses?
What are the 3 different types of NTs and examples:
Huge diversity in the variety of neurotransmitters, and their receptors - including amino acids, amines and neuropeptides
Amino acid neurotransmitters (NTs) include: Glutamate - v. important excitatory NT in the brain, GABA (gamma amino butyric acid) - v. important inhibitory NT in the brain, Glycine (gly) - inhibitory NT important in the spinal cord
Amine NTs include: Noradrenaline - important in the sympathetic NS, Dopamine - important in the brain, failure can lead to parkinson’s disease
Neuropeptide NTs include: opiod peptides - endorphines are actually peptides
The different NTs vary in abundance in different CNS tissue - generally amino acids present in mM conc., neuropeptides present in nM conc.
These different NTs can mediate between very fast or slower responses / effects
How is the CNS synapse activated?
[Basically A level content]
AP arrives at pre-synaptic knob, leads to influx of Na+, causes VG Ca2+ channels to open, increasing the concentration of Ca2+ in the cell to 200 micromolar
Stimulates exocytotic release of NTs from the synaptic vesicles (each contain 4,000 - 10,000 molecules)
Makes contact with the relevant receptors - causes excitatory or inhibitory effect depending on neurotransmitter and receptor
NTs reuptaken via a protein carrier molecule / protein channels in pre-synaptic neuron, reloaded again into vesicles so it can be reused
Na+/K+ pump reactivates to bring the neuron back to RMP
*take pic of A level and attach*
What are the 6 steps for the NT release process?
What is this process called?
Activation is Ca2+ dependent and requires rapid transduction
- Membrane depolarisation (i.e. AP arriving)
- VG Ca2+ channels open in the pre-synaptic terminal
- Ca2+ influx - electrical component, allows vesicles to dock onto pre-synaptic membrane, allows for priming of vesicles and then more Ca2+ allows for:
- Vesicle fusion and
- Vesicle exocytosis
- NT release
This process is called electromechanical transduction and it takes about 200 microseconds
Afterwards, vesicles are pinched off in a process called endocytosis, and are recyled
What is required for electromechanical transduction (AKA the NT release process)?
ATP! (many mitochondria in the pre-synaptic knob)
Calcium-dependent (Ca2+)
NT-containing vesicles to be docked on the presynaptic membrane
Protein complex formation between vesicle, membrane and cytoplasmic proteins to enable both vesicle docking and a rapid response to Ca2+ entry leading to membrane fusion and exocytosis
ATP and vesicle recycling
How do rapid release rates in synapses occur?
How are synaptic vesicles filled with NT?
What are the protein found on the surface of the vesicles and what do they allow?
Synaptic vesicles, which have protein pumps on their surfaces, are pre-filled with neurotransmitter and docked in the synaptic zone
Vesicular proteins are found on their surfaces - important in the docking process / fusion with membrane, allow them to interact with other proteins on the pre-synaptic mmbrane
Further Ca2+ influx enables for exocytosis
Black widow spider, Zn 2+, Tetanus, Botulinum
What do neurotoxins target in the synaptic process?
Use an example:
What is the difference between flaccid and spastic paralysis?
Usually vesicular proteins - interfere with the release process / release of NTs
Alpha latrotoxin - released from black widow spider, stimulates explosive NT release at cholinergic synapses leading to depletion (use up all the resources), causes respiratory arrest if targetting respiratory muscles
Zn2+ dependent endopeptidases inhibit transmitter release
Tetanus toxin, an endopeptidase released from C. tetani - breadown in cholinergic transmission leading to loss of functionality of skeletal muscles = paralysis
Botulinum toxin produced by C. Botulinum - flaccid paralysis = loss of muscle function
Flaccid = muscles relaxed + cannot move, spastic = too much contraction + cannot move
Choose between ion channel receptor and G-protein coupled receptor
Which receptors are fast / which are slow in transmission? (2 classes / types of receptors)
Key features of the G-protein coupled receptor? How does the G-protein receptor carry out its action?
Neurotransmitter action is defined by receptor kenetics
Ion channel receptor e.g. Glutamate = fast, can be excitatory or inhibitory (millisecond responses)
G-protein coupled receptor = slow (seconds / minutes). have 7 transmembrane segments, which are alpha helices of a protein that spiral through the lipid bilayer
When the G-protein couples receptor is activated by the NT, must link onto G protein first, which then binds onto effector cell to carry out their action
Examples of effectors include enzymes or channels
So why are the G-protein coupled receptors slower?
What are some examples of fast and slow receptor sites?
What are the 2 types of ACh receptors?
They have to pick up the G-protein once activated by the NT
Ion channel receptors (fast) - e.g. CNS: Glutamate, GABA; NMJ: Nicotinic ACh
G-protein coupled receptors (slow) - e.g. CNS and PNS: Muscuranic ACh receptors, dopamine, noradrenaline, serotonin, neuropeptides
Nicotinic
and Muscarinic = sit on the heart (reduce / slow down heart rate)
Which receptor is important in slowing down heart rate?
Muscarinic ACh receptor
Which ions enter the post synaptic neuron depending on excitatory or inhibitory effect?
How are distinct functional properties achieved?
Excitatory = Na+ influx - depolarisation e.g. glutamate
Inhibitory = Cl- influx - hyperplarisation e.g. GABA or Gly
Multiple subunit combinations - each receptor has 5 subunits, and different combinations produces different receptor subtypes
What is seen on a graph with membrane potential and time if electrodes are placed at the excitatory neurotransmitter receptor?
What is seen if electrodes are placed at the inhibitory NT post-synaptic receptor?
EPSP - excitatory postsynaptic potential
IPSP - inhibitory postsynaptic potential
What are the 2 main types of glutamate receptors?
Where do they get their names?
- AMPA - linked to Na+ channels - fast, excitatory receptors, rapid onset and offset - rapidly opened and closed. Oversitmulation = switched off + desensitised
- NMDA - linked to Ca2+ and Na+ channels - slower component for excitatory transmission, serve as coincidence detectors - important for learning and memory in the hippocampus. For it to be activated, requires another input to depolarise the cell first (cannot be activated on their own)
The agonists (chemical that binds to a receptor and activates it) that they are stimulated by
What occurs if there is over-activity of glutamate in the synapses within the brain?
Which NT normally counteracts the effects of glutamate?
Increased EEG activity - can cause seizures
Delayed increase in glutamine levels due to metabolism of glutamate in the brain
GABA balances out glutamate, if there is a reduction in GABA or it is not functioning, there is excess glutamate activity as it is not being counteracted efficiently
What sort of population health burdens does epilepsy cause?
What happens at the inhibitory CN synapse? e.g. using GABA
- GABA formed by decarboxylation of glutamate by GAD (glutamic acid decarboxylase)
- GABA is released and it binds to its post-synaptic receptors reversibly, causing Cl- influx in post-synapti neuron
- GABA then needs to be inactivated, reuptake of GABA by GABA transporters into the glial cells and also pre-synaptic neuron
- GABA inside the glial cells is broken down by enzymes, GABA-transaminase, which forms succinate semialdehyde from the GABA
What are the 5 parts to the GABA receptor?
What is the structure of the GABAA receptor?
Pentameric organisation of the GABAA receptor
It is an ion channel linked receptor
