Drug Targets: Ion Channels and GPCRs

Question 1

What maintains the resting potential of a neuron?

Answer 1

Ion gradients (K+ inside, Na+ outside)
Selective permeability (higher K+ leakage)
Sodium-potassium pump (3 Na+ out, 2 K+ in)

Question 2

What happens when a neuron is stimulated?

Answer 2

If the threshold (-55mV) is reached, voltage-gated Na+ channels open, leading to a rapid depolarization (+30 to +40 mV)

Question 3

How does the neuron return to its resting state?

Answer 3

Voltage-gated Na+ channels close
Voltage-gated K+ channels open (K+ exit), causing repolarisation.
K+ channels close slowly, leading to temporary hyperpolarisation (-80 mV)

Question 4

What are the key types of ion channels?

Answer 4

Ligand-Gated - Open when bound by specific molecules (e.g., nicotinic acetylcholine receptor, GABAA receptor)
Voltage-Gated - Open in response to changed in membrane potential

Question 5

Why are voltage-gated ion channels important drug targets?

Answer 5

They regulate essential physiological functions and have mutliple drug-binding sites (e.g., Sodium channels targeted by anesthetics)

Question 6

How do bensodiazepines affect GABA receptors?

Answer 6

They enhance GABA receptor affinity, increasing chloride conductance and potentiating inhibitory effects, leading to sedation and anxiolysis

Question 7

What are the key structural features of GPCRs?

Answer 7

Extracellular N-terminus, intracellular C-terminus
7 Transmembrane domains
Long intracellular third loop for G-protein coupling

Question 8

How do GPCRs mediate cell signaling?

Answer 8

Ligand binding induces conformational change, activating intracellulat signaling cascades via G-proteins

Question 9

Why are GPCRs significant in pharmacology?

Answer 9

The human genome encodes 400 GPCRs: they regulate diverse physiological processes and are major drug targets

Question 10

Where do GPCR ligands bind?

Answer 10

Binding sites vary and induce transmembrane helices, N-terminus, and extracellular loops