Lecture 4: Neurotransmitters and Pharmacology Flashcards

1
Q

What does information transfer across the synapse require?

A

Release of neurotransmitters and interaction with postsynaptic receptors

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2
Q

What are key features of synaptic transmission?

A
  • rapid timescale
  • diversity
  • adaptability
  • plasticity
  • learning and memory
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3
Q

What do the spines on dendrites do?

A

Increase surface area for more synaptic connections

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4
Q

How does the way the information is being transferred change?

A

The transmission is electrical in the pre-synaptic neurone before becoming chemical neurotransmission when it passes across the synapse and then it returns to electrical transmission in the post-synaptic neurone

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5
Q

What are the 3 stages of synaptic transmission?

A
  1. Biosynthesis, packaging and release of neurotransmitter
  2. Receptor action
  3. Inactivation
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6
Q

What can neurotransmitters be?

A
  • amino acids (e.g. glutamate, GABA)
  • amines (noradrenaline, dopamine)
  • neuropeptides (e.g. opioid peptides)
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7
Q

What is the most important excitatory neurotransmitter?

A

glutamate

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8
Q

What is the most important inhibitory neurotransmitter?

A

GABA

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9
Q

Which inhibitory neurotransmitter is present in the spinal cord?

A

glycine

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10
Q

What is considered a rapid effect or slower effect?

A
Rapid = us - ms
slower = secs
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11
Q

What does neurotransmitter release rely on?

A

increase in intracellular Ca2+ (200um) - this occurs by opening of Ca2+ ion channels

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12
Q

What in the presynaptic neurone provides the source of neurotransmitter?

A

synaptic vesicles

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13
Q

Outline the steps that lead to neurotransmitter release.

A
  1. membrane depolarisation
  2. Ca2+ channels open
  3. Ca2+ influx
  4. Vesicle fusion
  5. Vesicle exocytosis
  6. Transmitter release
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14
Q

What is the process called from the Ca2+ channels opening to transmitter release?

A

Electrochemical transduction

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15
Q

What are the synaptic vesicles?

A

Vesicles docked in the synaptic zone filled with neurotransmitter

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16
Q

What are the proteins on synaptic vesicles called and what are they important for?

A

Vesicular proteins - important in docking/fusion process and exocytosis

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17
Q

What are vesicular proteins the target of?

A

Neurotoxins

18
Q

What do Zn2+ endopeptidases inhibit?

A

transmitter release

19
Q

What does Tetanus toxin C tetani cause?

A

paralysis (breaks down skeletal muscle)

20
Q

What does botulinum toxin C botulinum cause?

A

flaccid paralysis (muscles lose functionality)

21
Q

What does alpha latrotoxin (from black widow spider) do?

A

Stimulates ACh release and cholinergic transmission to depletion

22
Q

Outline transmitter release requirements.

A
  • calcium dependent
  • transmitter-containing vesicles to be docked on 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 (lots of mitochondria)
23
Q

How is neurotransmitter action defined?

A

By receptor kinetics

24
Q

What 2 receptors could a neurotransmitter bind to?

A
  • ion channel receptor

- G protein coupled receptor

25
Q

What do ion channel receptors mediate?

A
  • Fast response (msecs)

- mediate all fast excitatory and inhibitory transmission

26
Q

What do G-protein coupled receptors mediate?

A
  • slow response (secs/mins)

- effectors may be enzymes (adenyl cyclase, phospholipase C or channels e.g. Ca2+, K+)

27
Q

What are some examples of ion channel receptors?

A
CNS: glutamate, GABA
Neuromuscular junction (NMJ): ACh at nicotinic receptors
28
Q

What are some examples of G-protein coupled receptors?

A

CNS and PNS: ACh at muscarinic receptors, dopamine (DA), noradrenaline (NA), serotonin (5HT) and neuropeptides (e.g. enkephalin)

29
Q

What are ion channel-linked receptors?

A

multiple subunit combinations-distinct functional properties

30
Q

What are some types of ion channel-linked receptors?

A
  • nicotinic cholinergic receptors (nAChR)
  • glutamate (GluR)
  • GABA (GABAR)
  • Glycine (GlyR) receptors
31
Q

What ion causes hyperpolarisation?

A

Cl- (makes resting potential even more negative so it’s harder to activate/propagate an action potential)

32
Q

What is an EPSP?

A

excitatory postsynaptic potential (excitatory neurotransmitter receptor)

33
Q

What is an IPSP?

A

inhibitory postsynaptic potential (inhibitory neurotransmitter receptor)

34
Q

What are the 2 different glutamate receptors?

A
  • AMPA receptor

- NMDA receptor

35
Q

What is the AMPA receptor for?

A
  • majority of fast excitatory synapses
  • rapid onset, offset and desensitisation
  • Na+ influx
36
Q

What is the NMDA receptor for?

A
  • slow component of excitatory transmission
  • serve as coincidence detectors which underlie learning mechanisms
  • Ca2+/Na+
37
Q

Outline what occurs at an excitatory CNS synapse.

A

1) glutamate synthesised from glucose via TCA cycle and transamination
2) Glutamate reversibly binds post-synaptic receptors (linked to ion channels)
3) Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
4) Glutamate enzymatically modified by glutamine synthetase to glutamine in glial cell

38
Q

What can lead to seizures?

A

abnormal cell firing with excess glutamate in the synapse

39
Q

How can you measure electrical activity in the brain?

A

Electroencephalography

40
Q

What is epilepsy characterised by?

A

recurrent seizures due to abnormal neuronal excitability

41
Q

Outline what occurs at an inhibitory CNS synapse.

A
  1. GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)
  2. GABA reversibly binds post-synaptic receptors (Linked to ion channels)
  3. rapid uptake of GABA transporters (GATs)
  4. GABA enzymatically modified by GABA-transaminase to succinate semialdehyde in glial cell
42
Q

Which drugs facilitate GABA transmission?

A
  • antiepileptic
  • anxiolytic
  • sedative
  • muscle relaxant