L11 - Myocardial Mechanics Flashcards
How is excitation coupled to muscle contraction?
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
What is the sarcolemma?
Myocyte plasma membrane
What is the structure of the sarcolemma?
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
What is the sarcoplasmic reticulum?
Fluid filled membranous sac surrounding each myofibril
Ca store
What selection of events leads to relaxation of muscle method?
- Low sarcoplasmic Ca2+ - 0.1μm
- Ca2+ pumps remove Ca from sarcoplasm and stores it in sarcoplasmic reticulum - 10nM
- 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 - Tropomyosin strand blocks myosin/actin binding site (Ca isn’t there to pull it off)
- Troponin holds tropomyosin in position
- Prevents myosin head from sticking to the actin molecule
- Muscle relaxed, extendable and soft
What selection of events leads to contraction of muscle method?
- Action potential propagates along transverse tubules activating voltage-gated Ca2+ channels
- Ca2+ rapidly diffuses out of SR into the sarcoplasm (10 fold increase)
- Ca2+ binds to troponin
- Conformational change in troponin/tropomyosin complex exposing myosin/actin binding site
- Myosin head sticks to binding site
- If ADP-Pi is available, crossbridge cycling occurs and the muscle shortens
Muscle tension is proportional to?
Number of cross bridges
Number of crossbridges is proportional to?
Sarcomere length
What is the optimum resting length of sarcomeres for maximum tension generation?
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
At what length sarcomere do you get maximal tension and crossbridge formation?
2.2um
How are 2.2um sarcomeres produced?
2.2 um sarcomeres are produced by 10-12mmHg filling pressure in the heart – e.g. pre-systole
How are myocytes regulates at the cellular level in cardiac muscle?
In skeletal muscle - fibre recruitment to increase contraction
In cardiac muscle – increase force each myocyte is producing
How can the length-tension relationship be measured?
- Record length of muscle
- Electrically twitch and record force
- Lengthen muscle
- Repeat steps 1-3 over a range of muscle lengths
- Plot force against muscle length
Papillary cardiac muscle and isotonic contraction
Muscle shortens
Tone remains constant
When are muscles stimulated to stretch and lift?
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
In isotonic contraction, the heavier the load the..?
Slower the contraction
There is an inverse relationship between shortening velocity and?
Afterload
How do you measure the velocity of shortening?
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
When is a change in contractility seen in the heart?
A change in contractility is shown when a heart changes its output per beat when the end diastolic volume is constant
When does contractility increase?
Increases when more crossbridges form per stimulus
Reflects the qualitative state of the actin/myosin crossbridges
Changes in contractility have?
Positive or negative inotropic effects
Changes in rate have?
Chronotropic effects
What does noradrenaline increase?
Increases Po and Vmax (maximal force and maximal velocity)
- Positive inotropic and chronotropic effects
What is the frequency-force relationship?
Inter-beat duration influences the force of contraction
Increased frequency leads to increased contractility
Increased frequency or extra beat leads to increased tension
What causes the frequency-force relationship?
Changes in Ca2+ availability
Accumulation of Ca2+ with each beat
