2.5: Neurotransmitters & pharmacology

Question 1

What is synaptic transmission?

Answer 1

Information transfer across synapse requiring release of neurotransmitters and their interaction with postsynaptic receptors

Question 2

List 4 characteristics of synaptic transmission

Answer 2

Rapid timescale
Diversity
Plasticity
Learning and memory

Question 3

4 basic structures of neurones

Answer 3

Dendrites
Soma
Axon
Synaptic terminal

Question 4

Purpose of spines present on surface of dendrites

Answer 4

Protein molecules that increase the surface area for information reception

Question 5

What neuronal structure integrates all information coming into a neurone

Answer 5

Soma (cell body)

Question 6

3 steps that occur when a dendrite of one neurone receives an electrical impulse form another neurone

Answer 6

Information reception at dendrites
Integration (occurs at soma)
Rapid transfer (AP) - impulse passed along axon towards synaptic terminals

Question 7

What type of neurotransmission occurs at the synapse

Answer 7

Chemical neurotransmission

Question 8

What structures is neurotransmission restricted to?

Answer 8

Synapses

Question 9

3 things synapse consists of

Answer 9

Presynaptic nerve ending/terminal
Gap(synaptic cleft) ~ 20-100nm
Postsynaptic regions (dendrite or cell soma)

Question 10

3 stages of synaptic transmission

Answer 10

Biosynthesis, packaging and release of neurotransmitter stored in vesicles
Receptor action- activation of post-synaptic receptors
Inactivation - NT inactivated once it’s activated receptors on post synaptic terminal

Question 11

3 types of molecules that can be neurotransmitters + examples

Answer 11

Amino acids - glutamate, gamma-aminobutyric acid (GABA)
Amines - noradrenaline and dopamine
Neuropeptices -opioid peptides

Question 12

Single-most important excitatory neurotransmitter in the brain

Answer 12

Glutamate

Question 13

Single-most important inhibitory neurotransmitter in the brain

Answer 13

GABA

Question 14

Where is glycine most active (2)
Is glycine excitatory or inhibitory?

Answer 14

Spinal cord and brain stem
Inhibitory

Question 15

2 methods by which neurotransmitters are returned to the pre-synaptic terminal

Answer 15

Re-uptake via protein transport channel
Enzymatic degradation within synaptic cleft

Question 16

What is the source of neurotransmitter

Answer 16

Synaptic vesicles

Question 17

Outline process of neurotransmitter release

Answer 17

Membrane depolarisation lead to opening of Ca2+ channels
Ca2+ influx leading to docking of synaptic vesicles onto pre-synaptic membrane
Neurotransmitter released by exocytosis in synaptic cleft
Vesicle buds off and recycles forming new vesicles that can be reused

Question 18

2 things required for neurotransmitter release

Answer 18

Calcium influx
Rapid transduction

Question 19

What type of proteins on the vesicles and presynaptic membrane enable fusion and exocytosis?

Answer 19

SNARE proteins (vesicular proteins e.g. synapsin)

Question 20

Vesicular proteins are targets for

Answer 20

Neurotoxins (esp. those that interfere with NT release process)

Question 21

What does alpha larotoxin (neurotoxin) do?
(From black widow spider)

Answer 21

Stimulate NT release until depletion of NT leading to muscular paralysis

Question 22

Function of Zn2+ dependent endopeptidases

Answer 22

Inhibit transmitter release

Question 23

What does tetanus toxin cause ?
What bacteria produce it

Answer 23

Spasms and paralysis as GABA and glycine inhibited

Produced by Clostridium tetani

Question 24

What does botulinum toxin cause and how does this come about?

Answer 24

Flaccid paralysis - complete muscle relaxation

Cleaves peptide bonds of vesicular proteins leading to inactivation - docking, fusion, release of NT cannot occur

Question 25

What bacteria produces botulinum toxin (one of most powerful toxins)

Answer 25

Clostridium botulinum

Question 26

How can drug toxicity be measured

Answer 26

Minimum dosage required to kill a mouse

Question 27

What repossessed do ion channel linked receptors mediate?

Answer 27

All fast excitatory and inhibitory transmission

Question 28

What type of responses do G-protein coupled receptors mediate?

Answer 28

SLOWer than ion channel linked receptors

Question 29

What can the effectors of the response generated by G-protein coupled receptors be?

Answer 29

Enzymes or ion channels

Question 30

2 examples of responses where ion channel linked receptors are used

Answer 30

CNS - glutamate, GABA NMJ - ACh at nicotinic receptors

Question 31

Give examples of responses where G-protein coupled receptors are used

Answer 31

CNS and PNS - ACh at muscarinic receptors (heart) Dopamine, noradrenaline, serotonin and neuropeptides

Question 32

What does opening of Na+ channels via a glutamate molecule do to postsynaptic membrane potential

Answer 32

Increase for short time repolarisation

Question 33

What postsynaptic potential does an inhibitory NT (e.g GABA A) cause ?

Answer 33

IPSP ( inhibitory postsynaptic potential) caused by GABA A receptor —> Cl- influx hyperpolarisation

Question 34

2 types of ion-channel linked glutamate receptors and what they mediate

Answer 34

AMPA - FAST excitatory synapses, only Na+ permeable NMDA - SLOW component of excitatory transmission, coincidence detectors which underline learning mechanisms - permeable to Na+ and Ca2+ (HIPPOCAMPUS high density )

Question 35

Outline the process that occurs at an excitatory glutamate synapse

Answer 35

1) Glutamate synthesised from glucose via TCA cycle and transamination 2)Loaded into vesicles- released into synaptic cleft via exocytosis Glutamate reversibly binds postsynaptic receptors (AMPA and NMDA) 3) Rapid uptake of glutamate by excitatory amino acid transporters (EAATs) OR 4) Glutamate enzymatically modified by glutamine synthetase to glutamine in glial cells

Question 36

What does an EEG (electroencephalogram) measure

Answer 36

Electrical activity in brain

Question 37

Abnormal cell firing associated with excess glutamate leads to

Answer 37

Seizures Spikes on EEG

Question 38

What is epilepsy characterised by?

Answer 38

Recurrent seizures due to abnormal neuronal excitability

Question 39

Process that occurs at an inhibitory GABA synapse

Answer 39

1) GABA synthesised (pre-synaptic terminal) by decarboxylation of glutamate by glutamic acid decarboxylase [GAD] 2) GABA Reversibly binds to post-synaptic receptors (Cl- channels open, influx leading to hyperpolarisation) 3) Rapid uptake of GABA by GABA transporters (GATs) OR 4) GABA enzymatically modified by GABA-T (GABA transaminase) to succinic semialdehyde (glial cells and GABA nerve terminals)

Question 40

6 drugs facilitating GABA transmission.

Answer 40

Barbiturates Benzodiazepines Steroids Convulsants Zn 2+ Ethanol

Question 41

4 properties of drugs facilitating GABA transmission

Answer 41

Antiepileptic Anxiolytic Sedative Muscle relaxant

Question 42

How many subunits does the GABA A receptor have?

Answer 42

5 - pentameric

Question 43

4 examples of neurotoxins

Answer 43

Alpha latrotoxin Zn2+ dependent endopeptidases Tetanus toxin (C tetani) Botulinum toxin (C botulinum)

Question 44

Two types of neurotransmitter receptors

Answer 44

Ion channel-linked receptors G-protein-coupled receptors

Question 45

Two types of ion channel linked receptors

Answer 45

GABA receptor - Na+ glutamate receptor - Cl-