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ACEM Primary Written > Neurology: Physiology - Neurotransmitters > Flashcards

Neurology: Physiology - Neurotransmitters Flashcards

1
Q

What are the two types of receptor?

A
  1. Ionotropic (ligand-gated)
  2. Metabotropic (GPCR)
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2
Q

Four type of small molecule neurotransmitters

A

4 As:
1. Amino acids (glutamate, GABA, glycine)
2. ATP
3. ACh
4. MonoAmines (NA, adrenaline, dopamine, 5HT)

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3
Q

What are heteroceptors?

A

Receptors which respond to chemicals other than the release transmitter (e.g. NA binding to heteroceptor on cholinergic nerve to inhibit ACh release)

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4
Q

Describe homologous vs heterologous desensitisation

A

In respond to prolonged exposure to ligand, receptors undergo desensitisation in one of two ways:
- Homologous: only to ligand specific to receptor
- Heterologous: unresponsive to other ligands as well

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5
Q

How does reuptake of neurotransmitters occur?

A

Via high-affinity, Na+-dependent membrane transporters

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6
Q

Why is glutamate reuptake especially important?

A

Is an excitotoxin which can kill cells by overstimulating them (may play a role in stroke and neurodegenerative disease)

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7
Q

What are the two types of reuptake transporters?

A

One only for glutamate, and co-transports Na+ in and K+ out
Other co-transports Na+ and Cl-

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8
Q

What is the main excitatory neurotransmitter in the brain and spinal cord? What % of excitatory CNS neurotransmission does it account for?

A

Glutamate (~75% of CNS)

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9
Q

Describe the synthesis and reuptake of glutamate

A

Synthesised from a-ketoglutarate in Krebs cycle, via action of GABA transaminase
Glutamate released from nerve terminal and transported into glia via glutamate reuptake transporter, then converted to glutamine by glutamine synthetase -> diffuses back into nerve terminal and hydrolysed back to glutamate by glutaminase (can also be directly taken up back into nerve terminal from synapse via membrane transporters)

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10
Q

What are the three subtypes of ionotropic glutamate receptors and how does each function?

A

All ionotropic
1. AMPA: Na+ influx, K+ efflux
2. Kainate: Na+ influx, K+ efflux
3. NMDA: Ca2+ and Na+ influx

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11
Q

Where are AMPA receptors found?

A

In glia and neurons

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12
Q

Where are kainate receptors found?

A

In glia and neurons
Presynaptically on GABA-secreting neurons, postsynaptically various

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13
Q

What mechanism is the major basis for glutamate excitotoxicity?

A

Ca2+ influx (via NMDA receptor activation)

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14
Q

How are NMDA receptors activated?

A

By glutamate binding, but also requires glycine binding to facilitate
Receptor activation is also blocked by extracellular Mg2+ at normal membrane potential and so there must also be partial depolarisation by adjacent AMPA/kainate receptors

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15
Q

How does the speed of EPSPs generated by AMPA and kainate receptors vs NMDA receptors compare?

A

AMPA/kainate: fast EPSPs
NMDA: slow EPSPs

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16
Q

Where are NMDA receptors found and what is their role in the CNS?

A

In neurons only (not glia)
May play a role in memory/learning

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17
Q

How many types of glutamate receptors are there?

A

3 ionotropic (AMPA, kainate, NMDA) and 8 metabotropic

18
Q

What are the mechanisms by which the metabotropic glutamate receptors work?

A

Either by increasing IP3/DAG or decreasing cAMP

19
Q

What is the main inhibitory neurotransmitter in the brain and spinal cord?

A

Brain: GABA
Spinal cord: glycine

20
Q

Describe the synthesis, reuptake and metabolism of GABA

A

Synthesised from glutamate by glutamate decarboxylase (GAD)
Metabolised to succinate in the Krebs cycle by GABA-T
Reuptake via GABA transporter (with transport into vesicles via VGAT)

21
Q

Describe the location and mechanism of action of the three GABA receptor subtypes

A

GABA(A): widely distributed in CNS, ionotropic and allows Cl- influx to produce fast IPSP
GABA(B): widely distributed in CNS, metabotropic with Gi inhibiting adenylyl cyclase resulting in increased K+ efflux, and G0 inhibiting Ca2+ influx
GABA(C): exclusively in retina, ionotropic and allows Cl- influx to produce fast IPSP

22
Q

What is the purpose of the chronic low-level stimulation of GABA(A) receptors by GABA in the CNS interstitial fluid?

A

Decreases “noise” (incidental discharge)

23
Q

On what receptor and to what subunit do benzodiazepines bind to exert their effects?

A

a subunit on GABA(A) receptors

24
Q

To what receptor do barbiturates bind to exert their effects?

A

Bind GABA(A) as agonist
Bind and inhibit AMPA

25
Q

Is glycine an excitatory or inhibitory neurotransmitter?

A

Does both

26
Q

How does glycine exert its excitatory and inhibitory effects?

A

Excitatory: permissive action on glutamate transmission via NMDA binding
Inhibitory: direct inhibition (primarily in brain and spinal cord) via pentameric Cl- channel

27
Q

What neurotransmitter is antagonised by strychnine? How does this present clinically?

A

Glycine
Causes convulsions, muscle hyperactivity

28
Q

Five sites that acetylcholine functions as a neurotransmitter

A
  1. Neuromuscular junctions
  2. Autonomic ganglia
  3. Postganglionic parasympathetic nerve-target organ junctions
  4. Some postganglionic sympathetic nerve-target organ junctions
  5. Basal forebrain and pontomesencephalic cholinergic complexes in the brain
29
Q

For which nerves in the CNS does acetylcholine act as a neurotransmitter?

A

All nerves EXITING the CNS: cranial nerves, motor neurons, preganglionic nerves

30
Q

Describe the synthesis and metabolism of acetylcholine

A

Synthesised from choline and acetyl CoA by choline acetyltransferase (ChAT) -> forms ACh (CoA taken up by mitochondria for reuse)
Hydrolysed to choline and acetate via acetylcholinesterase in synaptic cleft (choline reabsorbed)

31
Q

What two types of acetylcholine receptors are there? Where is each found?

A
  1. Muscarinic: found within brain, and in smooth muscle and glands
  2. Nicotinic: found in skeletal muscle at NMJ [N(M)], and in CNS and autonomic ganglia [N(N)]
32
Q

Where are many of the CNS ACh receptors located and what is their function?

A

Presynaptically on glutamate-secreting neurons to facilitate release

33
Q

Describe the five subtypes of muscarinic receptor: their distribution and mechanism of action

A

M1: found in CNS and autonomic ganglia, increases IP3/DAG to increase Ca2+
M2: found in heart, decreases cAMP to increase K+
M3: found in smooth muscle and glands, increases IP3/DAG to increase Ca2+
M4: found in CNS, decreases cAMP to increase K+
M5: found in CNS, increases IP3/DAG to increase Ca2+

(Can’t EVEN cAMP, ODD and DAGgy)

34
Q

Name one agonist and one antagonist of muscarinic receptors

A

Agonist: muscarine (from toadstools)
Antagonist: atropine

35
Q

What is the structure and mechanism of action of nicotinic receptors?

A

Pentameric ligand-gated ion channels that increase Na+ influx to produce depolarisation

36
Q

Where is serotonin found in its highest concentrations?

A

Platelets
GIT (enterochromaffin cells and myenteric plexus)
Midline raphe nuelci in brain (lower concentrations)

37
Q

Describe the synthesis, release and metabolism of 5HT

A

Synthesised from the essential AA tryptophan
- Tryptophan -> 5-hydroxytryptophan via tryptophan hydroxylase (rate-limiting step)
- 5-hydroxytryptophan -> 5HT via L-amino acid decarboxylase
- Transported into vesicles for release by VMAT

Reuptake of released 5HT occurs via SERT membrane transported
- Then either repackaged in vesicles or metabolised to 5-HIAA via MAO

38
Q

What is the clinical significance of 5-HIAA?

A

Urinary metabolite which can be used to measure 5HT metabolism

39
Q

How many classes of 5HT receptor are there and what is their structure and function?

A

All except 5HT3 are GPCRs
5HT3 is an ionotropic receptor which increases Na+ influx

40
Q

What is the clinical relevance of 5HT3?

A

Role in vomiting (present in GIT and in area postreme of brain)

41
Q

What is the role of 5HT2A receptors?

A

Cause platelet aggregation and smooth muscle contraction

ACEM Primary Written (160 decks)

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