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Advanced Molecular Cell Biology > 2 - Ligand Gated Ion Channels > Flashcards

2 - Ligand Gated Ion Channels Flashcards

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1
Q

What are ion channels?

A
  • Transmembrane proteins that span the membrane from one end to the other.
  • They are specific.
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2
Q

What are the main structural features of ion channels?

A
  • 2 or more helices that cross the lipid bilayer.
  • 2-6 subunits, that usually surround the pore.
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3
Q

What are ion channels classified based on?

A

Their gating mechanism and the ion selectivity of the pore.

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4
Q

What are some of the feature of a simple potassium ion channel?

A
  • Transmembrane helicase structures form a p-loop structure.
  • Forms a gate which is closed when in a resting state on the cytoplasmic side.
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5
Q

What do Na+ and K+ do in excitable cells?

A

Create action potentials.

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6
Q

What does Ca+ do after being transported into the cytoplasm?

A

causes a 2nd messenger to elicit a cellular response.

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7
Q

How are voltage gated ion channels different to ligand gated ion channels?

A
  • They have additional helices, S1-4 form a separate voltage sensing domain that is lateral to the subunits.
  • They have large polypeptides that extend into the cytoplasm.
  • they have plugging mechanisms.
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8
Q

What are transient receptor potential (TRP) channels?

A

Channels similar to voltage gated channels but have developed to detect stimuli such as chilli.

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9
Q

What are ligand gated channels controlled by?

A

The binding of a ligand

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10
Q

What happens when calcium binds to calmodulin?

A

the channels close and it creates negative feedback

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11
Q

What are the categories of extracellular ligand gated ion channels?

A

Pentameric (Nicotinic) - 4 transmembrane domains, 5 subunits including the pore
Tetrameric (Glutamate) - 3 transmembrane domains, 4 subunits including the pore.
Trimeric (ATP P2X) - 2 transmembrane domains, 3 subunits including the pore.

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12
Q

Features of Pentameric Assembly (cys-loop type)

A
  • Includes nicotinic acetylcholine receptors (nAchRs)
  • Subunits can move to make more space for ions to move through the channel
  • large external facing N domain and an intracellular loop between M3 and M4.
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13
Q

What no neuronal nAchRs exist as?

A

a2-10 and b2-4, each with different affinity depending on location and composition.

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14
Q

What is significant about a4 and a2?

A
  • They are expressed abundantly in the hippocampus and the cortex with high affinity to nicotine and varenicline.
  • Chronic expose to these chemical leads to upregulation of the receptors, which is linked to nicotine addiction.
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15
Q

What do mutations in nAchRs cause?

A

autosomal dominant nocturnal frontal lobe epilepsy. (ADNFLE)

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16
Q

How does enhanced receptor function cause ADNFLE seizures?

A

By increased nicotinic mediated transmitter release.

17
Q

What is another cause of ADNFLE seizures?

A

Mutation in the M2 region of the a4 neuronal nicotinic subunit.

18
Q

Features of Tetrameric Assembly (Glutamate receptors)

A
  • Similar structure to KcsA except the pore is inverted.
  • Forms as as dimer, the ligand binding sit closes when occupied.
  • Vital to every aspect of brain function and dysfunction contributes to human diseases.
19
Q

How does diversity in glutamate receptors come about?

A

From the difference in the way RNA is processed in the cell during RNA splicing.

20
Q

What are the 2 isoforms of glutamate receptors (eg AMPAR)?

A

Flip and flop

21
Q

What is the main difference between flip and flop?

A

Flop is faster in terms of desensitisation rate and reduced current response to glutamate.

22
Q

What contributes to the diversity of glutamate receptors?

A

Multiple genes, splicing and mRNA editing.

23
Q

What is the function of AMPA receptors?

A

Mediate fast excitatory synaptic transmission in the central nervous system.

24
Q

What is the function of NMDA receptors?

A

They are involved in learning and memory, they are also slower than other isoforms.

25
Q

What is the function of Kainate receptors?

A

Similar to AMPA receptors but have less of a role at synapses linked to schizophrenia, depression and huntingtons.

26
Q

What does the dysfunction of RNA modification lead to?

A

pathologic conditions.

27
Q

What does the downregulation of GluA2 Q/R editing in the neurons of ALS patients lead to?

A

An increase in Ca2+permealble AMPA receptors which causes damage due to glutamate excitotoxicity.

28
Q

In glioblastoma what correlated with increased malignancy?

A

Decreased ADAR2 activity and in increase in Ca2+ pathway promoting proliferation and tumorigenesis this was reversed when GluA2 Q/R was edited.

Advanced Molecular Cell Biology (19 decks)

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