Desensitisation and Ion channels

Question 1

Describe desensitisation

Answer 1

response to drug decreases when administered continuously or repeatedly

Two types
- Tachyphylaxis
- Tolerance

Question 2

Tachyphylaxis

Answer 2

response to drug diminishes very rapidly

neurotransmitter depletion, receptor phosphorylation

Question 3

Tolerance

Answer 3

response to drug decreases over days or weeks

decreased receptor number, physiological changes

Question 4

Describe the mechanisms of desensitisation

Answer 4

1. Change in receptors - ion channel receptors, display rapid desensitisation, conformational change
2. receptor translocation
3. Exhaustion of mediators
4. Altered drug metabolism
5. Physiological adaptation (homeostasis)
6. Active extrusion from cells (cancer chemotherapy) - actively remove drug

Question 5

Describe the physiology of ion channels

Answer 5

Ions can’t penetrate the cell membrane

Cells maintain a negative internal potential of –30 to –80mV
under resting conditions

Ion channels open/close to regulate ion flow
- regulates via electrochemical gradient and membrane potential

Question 6

examples of ion channel receptors

Answer 6

GABA ion channel receptor
Nicotinic acetylcholine receptor
5-HT

Question 7

Describe the structure of ion channel receptors

Answer 7

4-5 membrane spanning subunits
- intra and extracellular regions
- membrane spanning section

Subunits - alpha, beta, gamma, delta, etc.

Subunits composition of a channel determines which agonists can bind and which ions can cross

Question 8

Subunit structure of an ion channel

Answer 8

• 4 membrane-spanning a-helices
• Amino and carboxyl ends located extracellularly
• Binding domain

Question 9

Describe the transduction mechanisms of ion
channel receptors

Answer 9

depolarisation or hyperpolarisation

Question 10

Explain the interaction of a ligand with an ion channel receptor

Answer 10

e.g Nicotinamide acetylcholine receptor

• Two agonist molecules bind to 2 a-subunits
  -> required to activate the receptor
• 5 subunits turn slightly in relation to each other
• channel opens allowing for the entrance of Na+
  *causes muscle contraction

Question 11

the subsequent biological effect of ligand-receptor binding - NAR

Answer 11

open ion channel influx of Na+ = muscle contraction

Question 12

Predict the effect of stimulating ion channel receptors