Lecture 6: Signal Transduction

Question 1

Describe ligand-gated ion channels, how they differ from voltage-gated, give some examples

Answer 1

ligand-gated vs voltage-gated
ligand-gated: 5 subunits of 4TM domains, voltage-gated: 4 subunits of 6TM domains
can be direct or indirect gating for ligand-gated, non-specific
channels or receptors

Question 2

Describe and give examples of the difference between direct and indirect gating

Answer 2

direct: ion channels (ionotropic), ex. nicotinic AchR in neuromuscular junction
indirect: GPCR (metabotropic) ex. muscarinic AchR in smooth muscle

Question 3

Describe ionotropic receptors

Answer 3

class of ligand-gated ion channel - NT binding creates conformational change to open pore

Question 4

Describe metabotropic receptors and their signalling cascade

Answer 4

act through second messengers, GPCR, 7 TM domains with extracellular ligand-binding site and intracellular G-protein binding site

ligand binds to GPCR, G-protein binds, GDP exchanged for GTP via GEF, alpha subunit dissociates from beta/gamma, both go to activate different effectors

Question 5

Describe the 3 effector molecules

Answer 5

Gs: activates adenylyl cyclase, converts ATP to cAMP, activates PKA
Gi: does the opposite
Can be found in SA nodes at the HCN channels affecting heart rate through NE binding to adrenergic beta1 receptor
Gt -transducin activates phosphodiesterase. converts cGMP to GMP, closes channels releasing glutamate therefore cell hyperpolarizes in response to light
Gq - Ach binding to M1 muscarinic receptor in smooth muscle around bronchi creates contraction, activates Phospholipase C, cleaves PIP2 into DAG and IP3, DAG activates PKA C and IP3 binds to receptors to initiate calcium release