Lecture 3: Modulation of Membrane Potential Flashcards
What are the two different types of synapses?
chemical and electrical
How do ligand-gated ion channels work?
neurotransmitter binds -> channel opens -> ions flow across membrane
How do GPCRs work?
neurotransmitter binds -> G-protein is activated -> G-protein subunits or intracellular messengers modulate ion channels -> ion channel opens -> ions flow across membrane
Are ionotropic receptors fast or slow?
fast
Are metabotropic receptors fast or slow?
slow
What are the different types of neurotransmitter?
Small Molecule Neurotransmitters
Acetylcholine
Amino Acids: Glutamate, Aspartate, GABA, Glycine
Purines: ATP
Catecholamines: Dopamine, Noradrenaline, Adrenaline
Indoleamines: Serotonin
Imidazoleamines: Histamine
Peptide Neurotransmitters
What are the three main classes of ionotropic receptors and what is their division based upon?
AMPA, NMDA and Kainate. They are divided on the basis of their pharmacology
divided into families based on their pharmacology
What is the subunit of a receptor determined by?
genes
What are the features of a receptor subunit?
amino terminus and carboxy terminus
transmembrane spanning domain
What do multiple receptor subunits form?
a pore / channel
How can different receptors be made?
different combinations of receptor subunits
What is the nature of AMPA channels? Will more sodium or potassium initially pass through these channels?
non-selective cation channels which allow equal passage of sodium and potassium -> initially larger proportion of sodium moving through the channel
What is the role of Magnesium in an NMDA receptor?
- Magnesium binding to NMDA receptor prevents calcium ions from flowing into the cell
- Depolarisation through ligand bonding results in the removal of the Mg2+ block
- This mechanism prevents excessive activation of the receptor
- Preventing excessive activation protects the cell from excitotoxicity
- Excitotoxicity can occur when too much calcium enters the cell
-Too much calcium can trigger cell death
Q: What is the relationship between AMPA and NMDA receptors?
- The AMPA receptor depolarises the postsynaptic membrane
- The depolarisation of the postsynaptic membrane activates the NMDA receptor
- Binding of glutamate to the AMPA receptor causes the release of Mg2+ from the NMDA receptor’s ion channel pore
- AMPA and NMDA receptors work together in mediating synaptic transmission and plasticity in the brain.
What is the nature of NMDA channels?
glutamate binding to NMDA receptor opens a channel that transmits Ca2+, Na+ and K+
What are glutamate ion channels made up of?
subunits which have three membrane-spanning domains and a re-entrant loop
most models predict four subunits making up an ion channel
How is glutamate removed from the synaptic cleft?
EATTs present on astrocytes transport glutamate into the cell so that it can be converted to glutamine via Glutamine synthetase and inactivated -> glutamine is then taken up by EATTs present on the presynaptic terminal and converted back to glutamate via Glutaminase
Why is Glutamate recycling important
Glutamatergic neurons can maintain very high firing rates
High Fidelity of signaling due to rapid removal of glutamate from the synaptic cleft.
What are the properties of Inotropic receptors?
- Are ligand-gated ion channels that open in response to the binding of a neurotransmitter.
- Rapidly alter the postsynaptic membrane potential by allowing the influx of ions such as Na+, K+, and Ca2+.
- Have a relatively short-lived effect on the postsynaptic neuron.
- Are involved in fast synaptic transmission.
What are the properties of Metabotropic receptors
- Are G protein-coupled receptors that initiate intracellular signalling pathways when a neurotransmitter binds to them.
- Alter the activity of ion channels or enzymes within the postsynaptic neurone, leading to slower and more prolonged effects.
- Can modulate the activity of multiple ion channels or enzymes simultaneously, allowing for greater regulatory control.
- Are involved in slower synaptic transmission and modulation of neural activity.
Are acetylcholine receptors ionotropic or metabotropic?
both
nicotinic receptor = ionotropic
muscarinic receptor = metabotropic
What are nicotinic receptors important for?
somatic movement
How is acetylcholine inactivated?
acetylcholinesterase breaks down ACh to acetate and choline
What are nicotinic receptors and what are they made up of?
non-selective cation channels
they are made of pentamers of four transmembrane spanning domains
