2 - Introduction & Multisubunit Receptors - Gray

Question 1

Describe the 4 features of a good signal

Answer 1

• small so can travel easily and quickly
• unique enough to relay defined signal and to be detected by correct R
• synthesised, altered and released quickly to switch ON signal
• degraded or re-sequestered quickly to switch OFF signal

Question 2

What are the types of ligands for cell surface receptors and give some examples

Answer 2

normally hydrophilic (peptide hormones eg insulin) or charged (acetylcholine, adrenaline)

Question 3

Ligand binding can alter… (3)

Which gives rise to changes in …..

Answer 3

• membrane potential
• protein kinase activity
• concn of intercellular 2nd messengers eg cAMP,CAs2+,IP3

overall changes in enzyme and or gene expression

Question 4

Give examples of when the same signalling molecule can induce different responses in target cells
draw diagrams

Answer 4

eg acetylcholine receptors
Muscarinic (GPCR);
- on heart muscle cell. binding of ACh leads to reduction in heart muscle contraction
- on salivary Gland cell. leading to secretions

• binding of mushroom toxin instead to both of these Rs can lead to 1) increase in heart rate -> heart attack? 2) secretions

Nicotinic;
- ACh binds to ion channel on skeletal muscle cell. 2 AChs required to open ion channel, causes influx of Na+ -> muscle contraction

• also responds to nicotine

Question 5

Draw a simple diagram and explain how a nicotinic acetylcholine receptor works

Answer 5

• ligand binding, conformational change, ion flows through, altering membrane electrical potential
  343 - 2

Question 6

Draw a diagram to summarise neuronal signalling

What type of signalling involves neurotransmitters?

Answer 6

paracrine

343 - 2 word

Question 7

Where are nictotinic acetylcholine Rs found? What substances bind them?

Answer 7

found in postsynaptic plasma membranes of neurones and at neuromuscular junctions

• bound by both nicotine and ACh . both have similar structure and charge distribution
• also bound by snake venom a-bungarotoxin. competes with ACh for binding to receptor. binds irreversibly, blocking ligand binding, channel can no longer open, leading to paralysis and respiratory failure

Question 8

Do the subunits in nicotinic acetylcholine Rs differ depending on where the R is located?

Answer 8

YES, different subunit combinations in muscle and neuronal type Rs

Question 9

Draw a diagram of the nicotinic acetylcholine R. including all the subunits as well as a birds eye view.
Describe the structure

Answer 9

343 - 2 word
pentameric structure - 5 related subunits (a2,B,y,delta)
each subunit spans the membrane 4 times
ACh binding site on the a subunit is the extracellular domain composed of a Cys residues

Question 10

Describe how the binding of ACh to the nicotinic ACh R causes an influx of ions

Answer 10

• ACh binds to 2 a subunits causing conformational change of all subunits
• M2 a helices change conformation upon this ACh binding. leading to the opening of the channel (the M2 a helices normally responsible for keeping channel closed)
• rings of -vely charged aa’s (Asp/Glu) within the receptor attract the Na+ through the pore

Question 11

Describe the whole process of muscle contraction starting from receiving signal at motor neurone.
Draw diagrams to explain every step of the process.

Answer 11

OCCURS AT NEUROMUSCULAR JUNCTION;
- action potential coming down axon causes influx of Ca2+ into axon. causing fusion of vesicles with plasma membrane and exocytosis of acetylcholine across the synapse to the muscle cell
- 2 ACh bind to the nicotinic ACh R, generating influx of Na+ ions into cell. transient depolarisation (outside > -ve)
- localised membrane depolarisation causes more channels to open causing further depolarisation when we get > Na+ flooding in
- at the threshold level, intracellular ion channels release Ca2+
- T tubule allows current to penetrate into the cell where it activates Ryanodine receptors which release calcium from intracellular stores (eg from sarcoplasmic reticulum)
(this release of Ca is what causes muscle contraction)

• Ca2+ binding to troponin causes a conformational change
• moves tropomyosin so that the myosin head can come into contact with the underlying actin
• myosin head associated with actin, swivels causing muscle contraction
• ATP hydrolysis resets myosin