S1: Control of Smooth Muscle

Question 1

What is the structure of smooth muscle?

Answer 1

• No rigid cellular structures to couple stimulation to contraction
• No striations

Question 2

Where is smooth muscle found in our body?

Answer 2

It is found in the ‘walls’ of tubular organs

e.g. blood vessels, GI tract, airways, uterus, bladder, eye

Question 3

Describe the contraction that smooth muscle produces

Answer 3

Slow, sustained, graded contraction

Question 4

Compare the strength of smooth muscle contraction with skeletal and cardiac

Answer 4

Relatively weak contraction (compared to skeletal and cardiac muscle)

Question 5

What nervous system innervates smooth muscle?

Answer 5

Innervated by the Autonomic Nervous System (ANS)

Question 6

Can smooth muscle contract my itself?

Answer 6

Yes it can have spontaneous contractions (myogenic)

Question 7

What are the transmitters released from post-ganglionic autonomic nerves onto smooth muscle cells?

Answer 7

Parasympathetic nerves: Acetylcholine (Ach)

Sympathetic nerves: Noradrenaline (Na)

NANC (non adrenergic non cholinergic nerves): Nitric Oxide (NO) - erection in parasympathetic

Adrenaline from adrenal medulla

Question 8

What initiates smooth muscle contraction?

Answer 8

It is initiated by an increase in cytosolic Ca2+ concentration.

Question 9

What 2 things increase the concentration of Ca2+?

Answer 9

1. Increase in Ca2+ influx from extracellular medium

2. Release of Ca2+ from internal Ca2+ stores (sarcoplasmic reticulum)

Question 10

Explain how Ca2+ influxes from the extracelluar medium

Answer 10

• Stimulation of G protein coupled receptors (Gq family)
• Depolarisation occurs-
  Action on ion channels (VGNa+ channels)
• This activates VGCCs which has a threshold of -40 mV
• Ca2+ influx down a steep concentration gradient

Question 11

Explain how Ca2+ is released from Ca2+ stores in the sarcoplasmic reticulum

Answer 11

• Stimulation of G protein coupled receptors (Gq family)
• IP3 is generated and binds to IP3 receptor of SR membrane
• IP3 goes under conformational change and an ion channel that is permeable to calcium opens
• Ca2+ flows out into cytosol down its concentration gradient

Question 12

What receptors does smooth muscle calcium influx use compared to cardiac/skeletal muscle?

Answer 12

Smooth muscle contraction uses IP3 receptors

Cardiac/skeletal muscle contraction uses ryanodine receptors

Question 13

How does a rise in cytosolic Ca2+ produce smooth muscle contraction?

Answer 13

1. Calcium binds to protein Calmodulin (CaM)
2. Calcium-CaM complex is a selective molecule that binds to Myosin light chain kinase (MLCK)
3. This increases the activity of MLCK and it phosphorylates myosin light chain (which is a contractile protein)
4. This allows actin/myosin filament cross bridge formation and contraction occurs

Question 14

What does MLC-phosphatase (MLCP) do?

Answer 14

It removes a phosphate from myosin light chain (MLC-P) in a reversible reaction

Question 15

What causes relaxation of smooth muscle cells?

Answer 15

Decrease in concentration of Ca2+

Question 16

What decreases concentration of Ca2+ in cytosol?

Answer 16

• Hyperpolarisation caused by K+ channel opening closes VGCCs
• Ca2+ uptake into SR (Ca2+ - ATP)
• Extrusion of Ca2+ from cell (Ca2+-ATPase) (Na-Ca exchanger)

Question 17

How many Na+ and Ca2+ are exchanged?

Answer 17

3 Na+ for 1 Ca2+

Question 18

How does decrease in concentration of Ca2+ stop contraction?

Answer 18

• Decrease in concentration of Ca2+
• This reduces MLCK activity so balance falls in favour of MLC-phosphatase (MLCP). Less phosphorylated myosin light chains (MLC-P) so less actin-myosin interactions.

Question 19

Explain excitatory neurotransmission to smooth muscle

Answer 19

Delayed, slow, sustained contraction due to tie taken to switch on and off Ca2+ stimulates contractile events

1. Release of excitatory transmitter (Ach, NA) binds to receptor - Junctional depolarising potential
2. Threshold for voltage gated calcium channels (VGCC) is overcome and VGCC open. There is an Ca2+ influx into the cell leading to muscle contraction
3. Open K+ channels so repolarisation occurs. VGCC close so there is a decrease in Ca2+ influx and muscle relaxes

Question 20

Explain inhibitory neurotransmission to smooth muscle

Answer 20

• Inhibitory mediator such as nitric oxide hyperpolarises smooth muscle by opening K+ channels (e.g. Corpus cavernosa) and a hyperpolarisation occurs (more K+ diffuses out of cell so inside is more negative)
  This closes VGCC so there is a decrease in the concentration of Ca2+ and relaxation occurs