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Fundamental Neuroscience > Acetylcholine > Flashcards

Acetylcholine Flashcards

1
Q

How is acetylcholine synthesised?

(3 marks)

A
  • Formed from choline and acetyl coenzyme A (acetyl CoA)
  • Catalysed by choline acetyltransferase (ChAT)

choline acetyltransferase

  • choline + acetyl CoA ⇔acetylcholine + CoA
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2
Q

What can happen if you block cholinergic activity?

A

Can cause muscular paralysis

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3
Q

Where is ChAT found?

A

In cholinergic neurons and is released as ACh

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4
Q

How can you experimentally identify cholinergic neurons?

A

Stain fo ChAT

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5
Q

What is the rate of ACh controlled by?

(2 marks)

A

Availability of precursors and rate of cell firing

Direct correlation between levels of ChAT and ACh

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6
Q

How is ACh released?

(3 marks)

A
  • ACh is stored in vesicles and moves inot vesicles by vesicular ACh transporters (VAChT)
  • VAChT is blocked by drug vesamicol which may reduce amount of ACh in vesicles to be released when neurons fire
  • But ACh in cytoplasm increases as it doesn’t affect rate of ACh synthesis
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7
Q

What is botulinum?

A

Toxin that inhbits ACh release - can grow anaerobically and can be present in out of date canned food

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8
Q

Outline the mechanism of Botulinum

A
  1. Inhibits ACh release at neuromuscular junction by preventnig fusion of synaptic vesicles w/ nerve terminal membrane
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9
Q

What are some of the dangerous effects of botulinum?

(2 marks)

A
  • Muscle paralysis
  • Produced by anaerobic bacterium Clostridium botulinura
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10
Q

What are some of the benefits of botulinum?

(3 marks)

A
  • Can be used to treat disorders characterised by involuntary muscle contractions
  • Used by dermatologists as ‘Botox’:
    • treats facial wrinkles as it casuses localised paralysis and reduces wrinkles for a few months
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11
Q

How is ACh inactivated?

(3 marks)

A
  • Acetylcholinesterase enzyme (AChE) degrades it post-synaptically into choline and acetic acid
  • AChE in presynaptic cells can metabolise excess ACh that may have been synthesised
  • AChE located on post synaptic membrane
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12
Q

What happens to choline after it has been reduced?

A
  • Considered biologically inactive and can be recycled and brought back to presynaptic region by choline transporter
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13
Q

What drugs block the choline transporter and what is seen in mutant mice with no choilne transporter at birth?

(3 marks)

A
  • Hemicholinium-3 (HC-3) - blocks it and reduces ACh production
  • Mutant mice - will die an hour after birth
  • Lack of ACh synthesis and release at NT junctions causes breathing difficulties
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14
Q

Does ACh bind to metabotropic or ionotropic receptors?

A

Both x

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15
Q

How and what drugs prevent the activation of ACh?

(4 marks)

A
  • Done by blocking AChE
  • Physoltigmine - crosses blood brain barrier and affects CNS
  • Neostigmine and pyridostigmine - synthetic analogues of physotigmine that DO NOT cross blood brain barrier
  • ^^^ reversible AChE inhibitors
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16
Q

What can some varities of ‘nerve gas’ do?

A
  • Cause ACh accumulation and overstimulation of cholinergic synapses, throughout CNS and PNS causing msucle paralysis and death by asphyxiation
17
Q

Where is ACh present in the sympathetic and parasympathetic nervous system respectively?

(2 marks)

A
  • Sympathetic: ACh present only preganglionically (uses NE from ganglion to target)
  • Parasympathetic: ACh present only in preganglionically and on target organ
18
Q

How many regions does ACh provide cholinergic innervation to in the brain?

A

8 x

19
Q

What kind of drugs are prescribed in the early stages of PD?

(2 marks)

A

Anticholinergic drugs - as need balance of DA and ACh

e.g. Benztropine mesylate

20
Q

Where do the cholinergic neurons found in the nucleus basalis project to?

A

Rostrally to neocortex and invovled in positive effect of ACh

21
Q

What is the basal forebrain cholinergic system and what does 192 IgG do to it?

(5 marks)

A
  • Origin of cholinergic innervation of cerebral cortex, hippocampus and other limbic structures
  • Uses selective neurotoxin 192 IgG - saporin:
    • 192 IgG monoclonal antibody binds specifically to surface protein on basal forebrain cholinergic neurons
    • When injected into BFCS, cholinergic interneurons take up the toxin
    • Causes those neurons to be destroyed and neighbouring non-cholinergic cells are spared
22
Q

What do the cholinergic neurons in the dorsal lateral pons influence?

(2 marks)

A
  • Excitatory influence on midbrain DA neuron firing
  • Mediated by post synaptic nicotinic cholinergic receptor
23
Q

What are the two types of cholinergic receptor?

(2 marks)

A

Nicotinic receptor: agonist is nicotine - an alkaloid (found on muscle cells at neuromuscular junction)

Muscarinic receptor - respond to muscarine - an alkaloid (some inhibit cAMP and stimulate K+)

24
Q

What do nicotinic receptors do?

(3 marks)

A
  • Ionotropic
  • ACh binds and channel opens Na+ and Ca2+ flood into neuron or muscle cell and membrane is depolarised
  • Nicotinic receptors mediate post excitatory responses in both CNS and PNS
25
Q

What characteristics do all nicotinic receptors have in common?

(3 marks)

A
  • 5 subunits: α β γ δ ε (subunits may change don’t know exact number of receptors)
  • 10 α subunits and 4 β subunits
  • Receptors in muscle cells have diferent composition than the ones in neurons
26
Q

What are the 3 types of nicotinic receptor?

A
  1. Muscle nicotinic receptor
  2. Neuronal α4β2 receptor
  3. Neuronal α receptor
27
Q

What happens when nicotinic receptors are subject to continuous agonist exposure?

(5 marks)

A
  • Become desensitised - channel remains closed despite agonist presence
  • After short time spontaneously resensitize and able to respond to agonist
  • Not all recpetors are desensitized, but produce persistant depolarisation of cell membrane
  • After long exposure to agonist depolarisation block occurs
  • Resting potential of membrane lost and cell can’t be excited until agonist removed and membrane repolarised
28
Q

Give an example of a nicotinic ACh receptor agonist.

(2 marks)

A
  • Succinlycholine:
    • Muscle relaxant: reistant to breakdown by AChE - stimulate nicotinic receptor induces depolarisation block
29
Q

Give an example of some antagonists to the nicotinic receptor.

(4 marks)

A
  • Mecamylamine -
    • antagonist that blocks nicotinic receptors both in CNS and a_utonomic ganglia_
  • D-turbocarcarine -
    • antagonist of muscle nictonic receptor and main ingredient of curare
30
Q

How many muscarinic receptors are there?

A

5 - all metabotropic tht operate via secondary messengers

31
Q

What does the activtation of muscarinic M3 cells stimulate the secretion of?

A

Secretion of insulin by β-cells

32
Q

Where are M5 receptors located and what do they do?

(3 marks)

A
  • Hippocampus, hypothalamus and midbrain DA areas:
    • contribute to excitatory effect on dopamine neurons mediated by nicotinic receptors
    • Involced in rewarding and dependence producing effects of abused drugs
33
Q

What can be seen in M5 receptor KO in mice and what does this suggest?

(2 marks)

A
  • Shows deficits in morphine and cocaine reward system
  • Suggest M5 receptor important in regulating drug abuse which doesn’t directly regulate the cholinergic system
34
Q

Where are peripheral muscarinic receptors located and what are they activated by?

(2 marks)

A
  • Cardiac muscle, smooth muscle and insulin secreting cells of the pancreas
  • Activated by ACh released from post ganglionic fibres of the parasympathetic NS
35
Q

Where is M2 receptor located and what does it do?

(2 marks)

A
  • In cardiac muscle - a peripheral receptor
  • Stimulation of parasympathetic NS slows HR and decreases contraction strength
36
Q

Where is M3 receptor found and what does it do?

(3 marks)

A
  • Smooth muscle (peripheral m receptor)
  • Activation causes contraction
  • Receptors mediate secretory responses of ANS e.g. lamination and salivation
37
Q

What are some of the muscarinic receptor agonists and what can high doses cause?

(5 marks)

A
  • Muscarine
  • Pilocarpine
  • Arecoline
    • Exaggerated parasympathetic responses
    • Cardiovascular collapse, convulsions, coma and death
38
Q

What is atropine?

(2 marks)

A
  • Antagonist of muscarinic receptors
  • Dilates pupils and reduces secretions that clog airways and counteract poisoning by choinergic agonists
39
Q

What is scopolamine and what does it do?

(3 marks)

A
  • Antagonist for muscarinic receptors
  • Therapeutic doses: drowsiness, euphoria, amnesia and dreamless sleep
  • From plants can be deadly aka nightshade and henbane

Fundamental Neuroscience (19 decks)

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