week 11: LGICS

Question 1

Multiple Choice
Q1. Which of the following is not a class of ligand-gated ion channels?
A. Pentameric LGICs
B. Tetrameric LGICs
C. Trimeric LGICs
D. ATP-gated ion channels

Answer 1

→ Answer: C

Question 2

Short Answer
Q2. What are the two main structural classes of ligand-gated ion channels and give one example of each?

Question 3

Multiple Choice
Q3. The M2 transmembrane domain of a pentameric LGIC is responsible for:
A. Ligand binding
B. Protein folding
C. Forming the ion channel pore
D. Signal transduction via G proteins

Answer 3

→ Answer: C

Question 4

Short Answer
Q4. Describe the conformational change that occurs when a ligand binds to a pentameric LGIC to open the channel.

Answer 4

→ Model Answer: Ligand binding causes rotation and tilting of the M2 pore-lining helices, moving hydrophobic residues away from the pore to allow ion flow.

Question 5

Multiple Choice
Q5. Which of the following is an inhibitory ligand-gated ion channel?
A. nAChR
B. AMPAR
C. GABA_AR
D. NMDA

Answer 5

→ Answer: C

Question 6

Q6. List two excitatory and two inhibitory LGICs, including their endogenous ligands.

Answer 6

→ Model Answer:

Excitatory: nAChR (ACh), 5-HT R (serotonin)

Inhibitory: GABA R (GABA), GlyR (glycine)

Question 7

Short Answer
Q7. Explain how subunit composition can alter the function of GABA_A receptors.

Answer 7

→ Model Answer: Different α, β, and γ subunit combinations affect GABA sensitivity, ion conductance, and pharmacological properties, allowing >1000 possible receptor isoforms.

VARIABLE DIVERSITY

Question 8

Scenario-Based
Q8. A mutation changes a GABA_A receptor’s α subunit to a variant with lower GABA affinity. Predict how this would affect neuronal excitability.

Answer 8

→ Model Answer: Reduced GABA affinity would lead to less frequent channel opening, decreased Cl⁻ influx, and reduced inhibition, increasing neuronal excitability.

Question 9

Multiple Choice
Q9. Benzodiazepines act on GABA_A receptors by:
A. Competing with GABA for the active site
B. Inhibiting GABA release
C. Increasing frequency of channel opening
D. Blocking the M2 domain

Answer 9

→ Answer: C

Question 10

Short Answer
Q10. Compare the action of benzodiazepines and barbiturates on GABA_A receptors.

Answer 10

→ Model Answer: Benzodiazepines increase the frequency of channel opening, while barbiturates increase the duration of opening; barbiturates pose higher overdose risk.

Question 11

Scenario-Based
Q11. A neuron has both AMPA and NMDA receptors. Describe the sequence of events following glutamate release at the synapse.

Answer 11

→ Model Answer: Glutamate binds AMPA receptors first, causing Na⁺ influx and depolarization. This depolarization expels Mg²⁺ from NMDA receptors, allowing glutamate and glycine to activate NMDA receptors and permit Na⁺/Ca²⁺ influx.Short Answer

Question 12

Q12. How does RNA editing affect AMPA receptor ion selectivity?

Answer 12

→ Model Answer: Editing at the Q/R site in the TM2 domain changes glutamine to arginine, reducing Ca²⁺ permeability.

Question 13

Q1. The two primary structural classes of LGICs are:
A) Dimeric and trimeric
B) Pentameric and tetrameric
C) Hexameric and tetrameric
D) Trimeric and ATP-coupled

Answer 13

→ Answer: B

Question 14

Q2. Pentameric LGICs typically have how many transmembrane domains per subunit?
A) 1
B) 2
C) 4
D) 6

Answer 14

→ Answer: C

1,2,3,4 X 5

Question 15

Q3. Which of the following is a tetrameric LGIC?
A) GABA_AR
B) Glycine receptor
C) NMDA receptor
D) 5-HT₃ receptor

Answer 15

→ Answer: C

Question 16

Q6. In pentameric LGICs, the ion channel pore is formed by:
A) M1 domain
B) M2 domain
C) M4 domain
D) Intracellular loop

Answer 16

→ Answer: B

Question 17

Q7. What conformational change occurs in LGICs upon ligand binding?
A) ATP hydrolysis
B) Rotation of M2 helices
C) Phosphorylation of C-terminus
D) Subunit dissociation

Answer 17

→ Answer: B

Question 18

Q11. Which LGIC is activated by glycine and selective for Cl⁻?
A) nAChR
B) NMDA receptor
C) GlyR
D) AMPA receptor

Answer 18

→ Answer: C

Question 19

Q12. Which LGICs are excitatory? (Select all that apply)
A) AMPA
B) NMDA
C) GABA_A
D) nAChR

Answer 19

→ Answer: A, B, D

Question 20

Q16. Which of the following changes would most likely increase the Ca²⁺ permeability of an AMPA receptor?
A) RNA editing at the Q/R site
B) Removal of Mg²⁺
C) Insertion of GluN2B
D) Use of a GluA2-lacking subunit

Answer 20

→ Answer: D

Question 21

Q17. What effect does subunit composition have on GABA_A receptor pharmacology?
A) No effect
B) Only changes Cl⁻ selectivity
C) Affects GABA sensitivity and drug binding
D) Determines receptor dimerization

Answer 21

→ Answer: C

Question 22

Q21. Benzodiazepines enhance GABA_A receptor activity by:
A) Directly opening the channel
B) Increasing GABA synthesis
C) Increasing frequency of Cl⁻ channel opening
D) Blocking the M2 pore

Answer 22

→ Answer: C

Question 23

Q22. Barbiturates differ from benzodiazepines because they:
A) Are partial agonists
B) Decrease GABA binding
C) Increase duration of channel opening
D) Do not affect GABA_A receptors

Answer 23

→ Answer: C

Question 24

🧠 1. Explain the differences in the mechanism of action of benzodiazepines and pentobarbital on GABA receptors. Why are benzodiazepines relatively safe, whereas pentobarbitone can be lethal?

Answer 24

Model Answer:

Benzodiazepines bind allosterically to GABA_A receptors, increasing the frequency of Cl⁻ channel opening only when GABA is present. This enhances inhibitory signaling without directly activating the receptor.

Pentobarbital (a barbiturate) also binds to GABA_A receptors but increases the duration of Cl⁻ channel opening and can directly activate the channel at high doses, even without GABA.

This difference makes benzodiazepines safer, as their effect is self-limiting and GABA-dependent, while pentobarbital can cause excessive CNS depression, leading to respiratory failure or death if overdosed.

Question 25

💉 2. Describe the mechanism of action of propofol on ligand-gated ion channels.

Answer 25

Model Answer: Propofol is a general anesthetic that enhances the function of GABA_A receptors. It increases Cl⁻ conductance by prolonging channel opening, similar to barbiturates. This enhances inhibitory synaptic transmission, leading to sedation, unconsciousness, and anesthesia. It may also affect glycine receptors and inhibit excitatory LGICs to a lesser extent, contributing to its anesthetic effect.

Question 26

⚡ 3. Describe the mechanism of activation of NMDA receptors. Include the role of voltage, Mg²⁺, and agonists.

Answer 26

Model Answer: NMDA receptors are ionotropic glutamate receptors that require: Glutamate binding (agonist) Glycine or D-serine binding (co-agonist) Membrane depolarization to remove a voltage-dependent Mg²⁺ block from the channel pore At resting potential, Mg²⁺ sits in the pore and blocks ion flow, even if glutamate is bound. Depolarization (usually via AMPA receptor activity) expels Mg²⁺, allowing the channel to open. The channel then conducts Na⁺, K⁺, and Ca²⁺, with Ca²⁺ influx playing key roles in plasticity (e.g., LTP).

Question 27

🧬 5. What is RNA editing and how can it be used to modify the functions of AMPA receptors?

Answer 27

Model Answer: RNA editing is a post-transcriptional modification where adenosine (A) is converted to inosine (I), which is read as guanosine (G). In the GluA2 subunit of AMPA receptors, this editing changes glutamine (Q) to arginine (R) at position 607 in the TM2 domain, which lines the channel pore. Unedited GluA2(Q) makes the AMPA receptor Ca²⁺-permeable, while edited GluA2(R) blocks Ca²⁺ influx due to the positive charge of arginine. This editing modifies ion selectivity, protecting neurons from excitotoxicity in mature brains by reducing Ca²⁺ entry through AMPA channels.

Question 28

MCQ 1: Which of the following correctly matches a ligand-gated ion channel with its structure and ligand? A) NMDA receptor – pentameric – glycine B) GABA_A receptor – tetrameric – glutamate C) GABA_A receptor – pentameric – GABA D) AMPA receptor – pentameric – acetylcholine

Answer 28

c

Question 29

What is a key difference between pentameric and tetrameric ligand-gated ion channels? A) Pentameric LGICs are voltage-gated; tetrameric are not B) Tetrameric LGICs always conduct Cl⁻; pentameric conduct Na⁺ C) Pentameric LGICs have 5 subunits and often conduct Cl⁻; tetrameric LGICs have 4 subunits and usually conduct Na⁺/Ca²⁺ D) Both types have the same subunit number but different ligand affinities

Answer 29

c

Question 30

How does ligand binding lead to channel opening in pentameric LGICs? A) It activates G-proteins to open a separate channel B) It causes a conformational change that rotates M2 helices and opens the pore C) It removes a voltage-dependent block from the pore D) It triggers ATP hydrolysis to energize the channel

Answer 30

b