S1: Receptor Mechanism II

Question 1

Name the two places where nicotinic receptors are found

Answer 1

1. Skeletal muscle which is involved in communication between motor nerves and muscle contraction (NMJ)
2. Autonomic ganglia which is a group of nerves lying outside brain/spinal cord. It is involved in communication between pre ganglionic and post ganglionic nerves

Question 2

Do nicotinic receptors produce fast responses?

Answer 2

Yes

Question 3

How do nicotinic receptors have different pharmacology at skeletal muscle or ganglia receptors?

Answer 3

Nicotinic receptors have slightly different structures at skeletal muscle and autonomic ganglia. They therefore have different pharmacology so different antagonist act at either skeletal muscle or ganglia receptors.

Question 4

What are the five protein subunits that make up nicotinic receptors at the NMJ?

Answer 4

a1 
a1
ɛ
B
𝛿

Question 5

What are the five protein subunits that make up nicotinic receptors at the autonomic ganglion?

Answer 5

a3
a3
B4
B4
B4

Question 6

How are nicotinic receptors activated at NMJ?

Answer 6

1. Conduction of action potential in motor nerves
2. Activation of VGCCs by depolarising (Na+ influx) which causes Ca2+ influx into presynaptic terminal
3. Calcium dependent release of acetylcholine into cleft
4. Acetylcholine activates nicotinic ligand-gated receptors

Question 7

What happens when nicotinic receptors are activated at NMJ?

Answer 7

Generation of excitatory junction potential. This activates VGNa channels which initiates action potentials. These are converted into contraction.

Question 8

How is the response at NMJ terminated?

Answer 8

Breakdown of acetylcholine by acetylcholinesterase (AchE)

Question 9

What is EJP?

Answer 9

EJP is excitatory junction potential. It is the discrete partial depolarisation of smooth muscle produced by stimulation of excitatory nerves.

Question 10

How is EJP produced?

Answer 10

Ach binds to nicotinic (igand gated) receptor. An ion channel opens and Na+ enters producing an EJP.

Question 11

How does acetylcholine-mediated EJP produces action potential?

Answer 11

The EJP produces more depolarisation by opening voltage gates sodium channels of the membrane stimulating an action potential

Question 12

How does acetylcholine-induced action potentials produce skeletal muscle contraction?

Answer 12

1. Action potential conducted to t-tubule (invaginations that allow precise electrical conduction to area of contraction in skeletal muscles) and this activates VGCCs
   
   2. VGCCs change their configurations and this opens the RyR. Direct coupling (when one opens the other opens) between VGCCs and RyR on sarcoplasmic reticulum (SR) where the opening of the RyR causes the release of Ca2+.
   3. Ca2+ binds to troponin- allows action-myosin interactions
   4. Myosin heads perform power
2. Contraction- actin filaments move towards centre of sarcomere

Question 13

What activates VGCCs on sarcoplasmic reticulum?

Answer 13

Action potential being conducted to t-tubule

Question 14

What causes the release of Ca2+ from SR?

Answer 14

VGCCs change their configurations and direct coupling opens the RyR. The opening of RyR causes the release of Ca2+.

Question 15

What is RyR?

Answer 15

Ryanodine Receptor. It is ligand gated.

Question 16

How does Ca2+ induce skeletal muscle contraction?

Answer 16

Calcium ions binds to troponin allowing actin-myosin interactions. Myosin heads perform power contraction- actin filaments move towards centre of the sarcomere.

Question 17

What initiates contraction of cardiac muscle?

Answer 17

Cardiac action potentials generated in specialised cells at sino-atrial node.

Question 18

What increases muscle contraction?

Answer 18

Activation of G portein coupled B1-adrenoreceptors

Question 19

What activates B1 adrenoreceptors in the heart?

Answer 19

Noradrenaline released from sympathetic nerves and circulating adrenaline released from adrenal medulla.

Question 20

Why is increasing cardiac muscle contraction important for ‘fight or flight’?

Answer 20

Increasing cardiac muscle contraction increases cardiac output so more blood is supplied to tissues. This is how we increase blood flow during excersize and maintains blood flow during a crises eg. haemorrhage

Question 21

How does stimulation of B1-adrenoreceptors increase contraction of cardiac muscle?

Answer 21

Noradrenaline/adrenaline binds to the B1 receptor and stimulates it. This activates the Gs pathway where adenylate cyclase is stimulated which increases cAMP molecules and increases PKA. PKA phosphorylates VGCCs which increases it’s activity causing Ca2+ influx, Calcium induced calcium release at SR occurs through direct coupling of RyR and VGCCs, The increase of Ca2+ activates troponin which increases contractility.

Question 22

What receptor increases heart rate?

Answer 22

B1-adrenoreceptor

B1-Gs

Question 23

What receptor decreases heart rate?

Answer 23

M2 receptor

M2-Gi

Question 24

What nerve stimulates M2 receptor in the heart?

Answer 24

Vagus nerve

Question 25

Do GaS-coupled receptors cause relaxation of smooth muscle?

Answer 25

Yes

Question 26

How do GaS-coupled receptors cause relaxation of smooth muscle?

Answer 26

Through the GaS pathway, protein kinase A is produced.

Protein kinase A inhibits myosin light chain kinase (MLCK) which decreases contraction and relaxes smooth muscle.

Question 27

What receptor and pathway causes contraction of smooth muscle?

Answer 27

M3 receptor is G protein couples and it uses the Gq pathway. (Gaq/11)