Compare B1 and B2 signalling

Question 1

Amount of β1 and 2 in healthy heart

Answer 1

• β1 = 75%

- β2 = 25%

Question 2

β1 signalling

Answer 2

• Ligand activates receptor
• Gs dissociates to αs and βγ
• αS activates AC
• AC produces cAMP
• cAMP activates PKA
• PKA Pi’s TnI, LTCC and phospholamban (PLB)
• Increases contractility

Question 3

β2 signalling

Answer 3

• Gs but also Gi (pertussis toxin-sensitive)
• Gi dissociates to αi and βγ
• αi subunit inhibits AC
• βγ subunit can ‘mop up’ Gs by mass action, and also produces downstream activation of MAPK
• αi also activates cPLA2

Question 4

phospholipase A2 (cPLA2)

Answer 4

• Cytosolic effector protein

- cAMP-independent enhancement of Ca-handling and contraction

Question 5

Suppression and compensation

Answer 5

• Efficient β1-AR-AC coupling suppresses β2-AR-cPLA2 via PKA

- cPLA2 may compensate for deficient B1 signalling

Question 6

Distribution and stimulation

Answer 6

• β1 mainly, lots in the base of the heart, SNS innervation so NOR
• β2 more in apex of heart, not as well innervated so circulating Ad