Signalling pathways

Question 1

How is force of contraction increased in heart? (+ve inotrophy)

Answer 1

Adrenaline/noradrenaline bind to B1 adrenoreceptors
GDP –> GTP on alpha S unit
ATP –> cAMP
Activate PKA
PKA phosphorylates V gated Ca2+ channels
Allow more Ca2+ to enter for next contraction

Question 2

How is smooth muscle contraction achieved?

Answer 2

Noradrenaline on a1 adrenoreceptors = vasoconstriction

Ach binding to M3 muscarinic = contraction in bronchioles (bronchoconstriction)

Question 3

What pathway do all smooth muscle contraction use?

Answer 3

GaQ protein activates phospholipase C
PIP2 cleaved into IP3 and DAG
Ca2+ intracellular increases (IP3 binds to receptors on ER)
PKC activated

Question 4

How is neurotransmitter regulated?

Answer 4

Depolarisation activates V gated Ca2+ channels
Ca2+ influx = neurotransmitter vesicles fuse with membrane
µ-opioid receptors can regulate V gated Ca2+ channels

Question 5

µ-opioid receptors example of Ca2+ regulation

Answer 5

Opioid binds to µ-opioid receptor (eg morphine)
GDP –> GTP on alpha i unit
Beta-gamma unit binds to V gated Ca2+ channels
Reduce Ca2+ influx and neurotransmitter release

Question 6

What happens when GDP –> GTP?

Answer 6

Alpha unit separates from beta-gamma unit

Question 7

3 key features of signal transduction

Answer 7

Diversity (subtypes of receptors, G proteins and effectors)
Specificity (specific ligand-receptor binding, G proteins and effector pathways)
Amplification (control, small changes = big changes in cellular behavious)