Lecture 3: Modulation of Membrane Potential

Question 1

What are the two different types of synapses?

Answer 1

chemical and electrical

Question 2

How do ligand-gated ion channels work?

Answer 2

neurotransmitter binds -> channel opens -> ions flow across membrane

Question 3

How do GPCRs work?

Answer 3

neurotransmitter binds -> G-protein is activated -> G-protein subunits or intracellular messengers modulate ion channels -> ion channel opens -> ions flow across membrane

Question 4

Are ionotropic receptors fast or slow?

Answer 4

fast

Question 5

Are metabotropic receptors fast or slow?

Answer 5

slow

Question 6

What are the different types of neurotransmitter?

Answer 6

Small Molecule Neurotransmitters
Acetylcholine
Amino Acids: Glutamate, Aspartate, GABA, Glycine
Purines: ATP
Catecholamines: Dopamine, Noradrenaline, Adrenaline
Indoleamines: Serotonin
Imidazoleamines: Histamine
Peptide Neurotransmitters

Question 7

What are the three main classes of ionotropic receptors and what is their division based upon?

Answer 7

AMPA, NMDA and Kainate. They are divided on the basis of their pharmacology

divided into families based on their pharmacology

Question 8

What is the subunit of a receptor determined by?

Answer 8

genes

Question 9

What are the features of a receptor subunit?

Answer 9

amino terminus and carboxy terminus

transmembrane spanning domain

Question 10

What do multiple receptor subunits form?

Answer 10

a pore / channel

Question 11

How can different receptors be made?

Answer 11

different combinations of receptor subunits

Question 12

What is the nature of AMPA channels? Will more sodium or potassium initially pass through these channels?

Answer 12

non-selective cation channels which allow equal passage of sodium and potassium -> initially larger proportion of sodium moving through the channel

Question 13

What is the role of Magnesium in an NMDA receptor?

Answer 13

• 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

Question 14

Q: What is the relationship between AMPA and NMDA receptors?

Answer 14

• 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.

Question 15

What is the nature of NMDA channels?

Answer 15

glutamate binding to NMDA receptor opens a channel that transmits Ca2+, Na+ and K+

Question 16

What are glutamate ion channels made up of?

Answer 16

subunits which have three membrane-spanning domains and a re-entrant loop
most models predict four subunits making up an ion channel

Question 17

How is glutamate removed from the synaptic cleft?

Answer 17

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

Question 18

Why is Glutamate recycling important

Answer 18

Glutamatergic neurons can maintain very high firing rates

High Fidelity of signaling due to rapid removal of glutamate from the synaptic cleft.

Question 19

What are the properties of Inotropic receptors?

Answer 19

• 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.

Question 20

What are the properties of Metabotropic receptors

Answer 20

• 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.

Question 21

Are acetylcholine receptors ionotropic or metabotropic?

Answer 21

both
nicotinic receptor = ionotropic
muscarinic receptor = metabotropic

Question 22

What are nicotinic receptors important for?

Answer 22

somatic movement

Question 23

How is acetylcholine inactivated?

Answer 23

acetylcholinesterase breaks down ACh to acetate and choline

Question 24

What are nicotinic receptors and what are they made up of?

Answer 24

non-selective cation channels

they are made of pentamers of four transmembrane spanning domains

Question 25

What are gap junctions composed of and what do they enable?

Answer 25

molecules such as connexins

electrical synapses

Question 26

How do electrical synapses work?

Answer 26

enable direct passage of ions between neurons -> this ionic movement alters the postsynaptic membrane potential

Question 27

Is there such thing as mixed synapses?

Answer 27

yes

Question 28

What are ionotropic receptors made of?

Answer 28

collections of protein subunits that interact to form a pore

Question 29

What is the effect of opening a non-selective ion channel dependent on?

Answer 29

the membrane potential and the transmembrane ion concentrations