Alpha/Beta/Calcium Channel Antagonists ***

Question 1

Describe the affinities of the catecholamines (adrenaline and noradrenaline) for α- and β-adrenoceptors.

Answer 1

• α-adrenoceptors - noradrenaline greater affinity than adrenaline
• Reverse for β-adrenoceptors.

Question 2

What are the major cardiac effects mediated by α- and β-adrenoceptors?

Answer 2

• α1- Vascular smooth muscle -vasoconstriction
• β1 - Heart-increase heart rate & myocardial contractility

Question 3

Describe vascular smooth muscle activation by the α1-adrenoceptor. PART 1

Answer 3

• AGONISTS - Catecholamines
• Calcium enters the cytoplasm through CAV channels located in caveolae
• Agonists acting through a GPRC can lead to the formation of IP3

Question 4

Describe vascular smooth muscle activation by the α1-adrenoceptor. PART 2

Answer 4

• Calcium entering through the CAV channel activates the ryanodine receptor (RYR), which release more calcium in CDCR
• IP3 formed by PLC activate IP3R, which also releases calcium. Raised intracellular calcium concentration

Question 5

Describe smooth muscle contraction. PART 1

Answer 5

• Increased intracellular Ca2+causes the binding of four Ca2+ions tocalmodulin (CaM),
• Activates MLCK- phosphorylates the regulatory light chain associated with each neck of the dimeric myosin II heavy chain

Question 6

Describe smooth muscle contraction. PART 2

Answer 6

• Conformational change of the myosin head
• Increases ATPase activity
• Interacts with actin
• Cross-bridge cycling and smooth muscle contraction.

Question 7

Describe activation of the cardiac muscle by the β1-adrenoceptor.

Answer 7

• Agonists e.g epinephrine and dobutamine bind to GPCR. cAMP forms
• cAMP activates PKA
• Phosphorylates IP3R and RYR2 - increased calcium release from SR into cytosol
• Free calcium in cytosol causes CICR through activation of RYR2
• Increased force of contraction

Question 8

What occurs when there is high calcium concentration at the following:
- SAN and AVN
- Cardiac myocytes

Answer 8

• Increased rate of depolarisation (chronotropy)
• Increased force of contraction (inotropy)

Question 9

Describe activation of the M2 receptors to decrease heart rate. PART 1

Answer 9

• Parasympathetic neurones send action potentials from medulla oblongata via vagus nerve
• Vagus nerve releases ACh and binds to M2 receptor on SAN and AVN - reduced pacemaker activity

Question 11

Describe activation of the M2 receptors to decrease heart rate. PART 2

Answer 11

• M2 receptors are Gi receptors - inhibit adenylate cyclase
• Decreased cAMP and PKA
• Decreased heart rate