4 - Ionotropic & Intracellular Receptors

What is an ionotropic receptor?

Receptor linked to an ion channel

What type of acetylcholine receptor is

- nicotinic (nAChR)

- muscarinic (mAChR)

ionotrophic

metabotrophic (G protein)

Types of nicotinic receotors (nAChR)

Muscle endplate nicotinic (neuromuscular junction)

Neuronal “ganglionic” nicotinic (ANS)

Which are always reversible: Agonist or antagonist reactions?

Agonist always reversible

antagonists can be both reversible and irreversible

How does the action of toxins work?

example of non-reversible reaction

a-bungarotoxin

Blocks nicotinic ACh receptors at NMJ

Stops muscle contractions

Brief structure of a nAChR

5 subunits
4 Transmembrane domains
ACh binds to alpha subunits

a-bungarotoxin vs d-tubocurarine

a-bungarotoxin —> irreversible

d-tubocurarine —> reversible

How does Curare work?

Example of a reversible reaction

d-tubocurarine

Blocks nAChR (REVERSIBLE)

Stops muscle contractions (used during surgery)

Then can be reversed

allosteric modulators (non-competitive inhibitor)

Substance that binds to cell receptor but binds on the other side
Still causes an effect

E.g. alcohol

Inverse agonist

Binds to the same site as the agonist but causes the opposite effect to the agonist

The GABA receptor is a type of which receptor?

ionotropic

GABA binds, activates receptor, allows chloride to pass through receptor & acts as an inhibitor

What type of hormones commonly activate intracellular receptors?

Steroid hormones

What is the action of an intracellular receptor? Is it a fast or slow acting receptor?

Alters transcription
Slow response

Describe the structure of an intracellular receptor

ligand binding domain
DNA binding domain
Transcription activating domain

How do intracellular receptors work?

1. Hormones cross plasma membrane & bind to cytoplasmic receptors

2. Hormone binding alters receptor conformation so it no longer binds inhibitor

3. Hormone-receptor complex translocates to nucleus

4. Hormone -receptor complex binds to DNA —> usually turns on transcription but can also turn it off

5. Cellular response is change in gene expression