L11 - Myocardial Mechanics

Question 1

How is excitation coupled to muscle contraction?

Answer 1

Electrical excitation triggers a set of events leading to muscle contraction
- There is a few ms delay
T-tubules and intercalated discs rapidly transmit action potentials in the myocardium

Question 2

What is the sarcolemma?

Answer 2

Myocyte plasma membrane

Question 3

What is the structure of the sarcolemma?

Answer 3

Thousands of invaginations – inward folding’s of sarcolemma forming transverse tubules
- Allows action potential to stimulate deep into myocyte simultaneously
- Allows faster contraction
Cisterns – at the end of the myofibril to store water

Question 4

What is the sarcoplasmic reticulum?

Answer 4

Fluid filled membranous sac surrounding each myofibril

Ca store

Question 5

What selection of events leads to relaxation of muscle method?

Answer 5

1. Low sarcoplasmic Ca2+ - 0.1μm
2. Ca2+ pumps remove Ca from sarcoplasm and stores it in sarcoplasmic reticulum - 10nM
3. Calsequestrin in sarcoplasmic reticulum binds to free Ca2+ lowering [Ca2+]SR
   a. Allows Ca pumps to work more efficiently allowing more Ca2+ to be stored in SR
4. Tropomyosin strand blocks myosin/actin binding site (Ca isn’t there to pull it off)
5. Troponin holds tropomyosin in position
6. Prevents myosin head from sticking to the actin molecule
7. Muscle relaxed, extendable and soft

Question 6

What selection of events leads to contraction of muscle method?

Answer 6

1. Action potential propagates along transverse tubules activating voltage-gated Ca2+ channels
2. Ca2+ rapidly diffuses out of SR into the sarcoplasm (10 fold increase)
3. Ca2+ binds to troponin
4. Conformational change in troponin/tropomyosin complex exposing myosin/actin binding site
5. Myosin head sticks to binding site
6. If ADP-Pi is available, crossbridge cycling occurs and the muscle shortens

Question 7

Muscle tension is proportional to?

Answer 7

Number of cross bridges

Question 8

Number of crossbridges is proportional to?

Answer 8

Sarcomere length

Question 9

What is the optimum resting length of sarcomeres for maximum tension generation?

Answer 9

Short sarcomeres - overlapping thin filaments - less tension generation
Long sarcomeres - reduced areas for crossbridge formation - less tension generation
At optimal length – highest number of actin/myosin binding sites available

Question 10

At what length sarcomere do you get maximal tension and crossbridge formation?

Answer 10

2.2um

Question 11

How are 2.2um sarcomeres produced?

Answer 11

2.2 um sarcomeres are produced by 10-12mmHg filling pressure in the heart – e.g. pre-systole

Question 12

How are myocytes regulates at the cellular level in cardiac muscle?

Answer 12

In skeletal muscle - fibre recruitment to increase contraction
In cardiac muscle – increase force each myocyte is producing

Question 13

How can the length-tension relationship be measured?

Answer 13

1. Record length of muscle
2. Electrically twitch and record force
3. Lengthen muscle
4. Repeat steps 1-3 over a range of muscle lengths
5. Plot force against muscle length

Question 14

Papillary cardiac muscle and isotonic contraction

Answer 14

Muscle shortens

Tone remains constant

Question 15

When are muscles stimulated to stretch and lift?

Answer 15

Muscle stretched by pre-load and stimulated to lift afterload

• Pre-load
• • Initial stretching
• • Sarcomere length increases
• • Indicated by ventricular end diastolic volume
• Afterload
• • Force against which the ventricles act to eject blood
• • Arterial blood pressure and vascular tone

Question 16

In isotonic contraction, the heavier the load the..?

Answer 16

Slower the contraction

Question 17

There is an inverse relationship between shortening velocity and?

Answer 17

Afterload

Question 18

How do you measure the velocity of shortening?

Answer 18

With varied pre- and afterloads
Increased preload gives increased maximal force (because of length-tension relationship)
For any afterload increase preload gives increased velocity
Vmax is constant

Question 19

When is a change in contractility seen in the heart?

Answer 19

A change in contractility is shown when a heart changes its output per beat when the end diastolic volume is constant

Question 20

When does contractility increase?

Answer 20

Increases when more crossbridges form per stimulus

Reflects the qualitative state of the actin/myosin crossbridges

Question 21

Changes in contractility have?

Answer 21

Positive or negative inotropic effects

Question 22

Changes in rate have?

Answer 22

Chronotropic effects

Question 23

What does noradrenaline increase?

Answer 23

Increases Po and Vmax (maximal force and maximal velocity)

- Positive inotropic and chronotropic effects

Question 24

What is the frequency-force relationship?

Answer 24

Inter-beat duration influences the force of contraction
Increased frequency leads to increased contractility
Increased frequency or extra beat leads to increased tension

Question 25

What causes the frequency-force relationship?

Answer 25

Changes in Ca2+ availability

Accumulation of Ca2+ with each beat