Neurotransmitters

Question 1

Describe the Structure of Neurons?

Answer 1

• Dendrites detect the input and are covered in spines
• Information propagates down the spine, integration occurs in the soma
• Action potential generated at Axon Hillock
• Synpatic cleft = 20-100nm
• Many mitochondria in the axon terminal to release neurotransmitter
• takes 2ms for the action potential to travel from one cell to the next

Question 2

What is the mechanism of neurotransmission?

Answer 2

• action potential activates Ca2+ channel
• Ca2+ enters nerve terminal and exocytosis of neurotransmitter
• ## Transporters remove neurotransmitter from terminal and they reenter vesicles

Question 3

Types of Neurotransmitters?

Answer 3

Amino Acid - glutamate, GABA, glycine

Amines - noradrenaline, dopamine

Neuropeptides - opoid peptides

• rapid or slow effects

Question 4

How does rapid release occur?

Answer 4

• lots of proteins docked in Axon terminal
• some docked in active zone
• alpha helices interaction between presynaptic membrane and the vesicle –> stable complex of vesicles .released by calcium
• nearby = high concentration of calcium channels
• when enters is detected by calcium sensor protein makes commplex undergo conformational change.

Question 5

Vesicular proteins and neurotoxins?

Answer 5

Tetanus = spastic paralysis - zinc dependent endopeptidases inhibit neurotransmitter release

Botulinum = Flacid paralysis

Alpha Latrotoxin = binds to vesicle protein at site of release prevents vesicle recycling and transmitter is depleted

Question 6

RECAP - Transmitter Release Requires?

Answer 6

Docking - Transmitter filled vesicles must be docked onto the presynaptic membrane

Protein Complex Formation - between vesicle, membrane + cytoplasmic proteins - allows vesicle docking and rapid response to Ca2+

ATP and vesicle recycling

Question 7

Describe Receptor Kinetics?

Answer 7

Ion Channel Receptor = FAST

GPCR = SLOW

Ion channel receptors mediate ALL fast excitatory and inhibitory transmission

Question 8

Examples of ion channel receptors + GPCRs

Answer 8

Ion Channel Receptor:

• Glutamate
• GABA
• Nicotinic Acetylcholine (Neuromuscular junction)

GPCR

• Muscarinic (neuromuscular junction)
• Dopamine
• 5-Hydroxytryptamine
• Neuropeptides (enkephalin)

Question 9

Types of Glutamate receptors?

Answer 9

AMPA receptors - FAST, rapid onset, offset, desensitisation NMDA - SLOW
need depolarisation and glutamate to bind, Na+ and Ca2+ influx.

Question 10

Formation of Glutamate?

Answer 10

• from intermediary metabolism
• Transamination of glutmate
• transporters on glial cells and presynaptic membrane cause uptake of glutamate
• there, glutamate is inactivated by glutamine synthase –> glutamine

Question 11

How is Epilepsy linked to Glutamate?

Answer 11

• due to abnormal release of glutamate –> hyperexcitability of cells
• 30% are refractory to treatment

Question 12

Describe the inhibitory synapse?

Answer 12

• GABA = main inhibitory neurotransmitter
• Synthesised by Glutamic Acid Decarboxylase (vitamin B6 enzyme0
• Transporters on Glial Cells + presynaptic neuron uptakes GABA (GAT)
• Inside, inactivated by GABA transaminase –> succinate semialdehyde –> TCA cycle

Question 13

Pharmacological action at the GABA receptor?

Answer 13

• anti-epileptics, sedatives, muscle relaxants
• binding site for benzodiazepines, barbituates.
• these alter the length of channel opening and frequency respectively