Myocardial mechanics Flashcards
What is the process of excitation-contraction coupling?
1) Electrical excitation from ALPHA motor neuron
2) Series of events including Ca2+ - delay in muscle contraction
3) T-tubules and intercalated discs rapidly transmit action potentials to the myocardium
Where are intercalated discs present?
In cardiac muscle
What is the sarcolemma?
The myocyte plasma membrane
What are t-tubules?
What do they allow?
Invaginations of the sarcolemma that dive deep into the myocyte
Allows action potentials to stimulate ALL parts of the muscle SIMULANEOUSLY
What does the action potential down the t tubules activate?
Sarcoplasmic reticulum
What is the sarcoplasmic reticulum?
What does it store?
Specialised type of SER
Fluid-filled membranous sac that surrounds each myofibril
Stores Ca2+
What is the structure of the SR?
- Voltage gated ion channels
- Cisterns - store the water
Where are the cisterns of the SR?
At the END of the myofibrils
In a triad:
- 2 cisternes
- 1 central T-tubule
What occurs in a relaxed muscle with Ca2+?
- Sarcoplasmic [Ca2+]
- Ca2+ pumps MOP UP calcium from the sarcoplasm and stores it in the sarcoplasmic reticulum
- Sarcoplasmic reticulum [Ca2+] ~10nm
Where is CALSEQUESTIN present?
What does it do?
Why is this advantageous?
Present in the SR
Binds to FREE Ca2+ - lowering [Ca2+]
Advantageous:
1) Makes it seem like low Ca2+ in SR
2) Pumps work more efficiently and quickly
3) More Ca2+ stored in the SR
4) More Ca2+ can be released during contraction
What are the additional proteins involved in muscle contraction?
1) Tropomyosin
2) Myosin and actin
3) Titin
4) Troponin
What does tropomyosin do?
- Covers the actin/myosin binding site
- Preventing the myosin head from sticking to the actin molecule
- Muscle remains relaxed
What does titin do?
Tethers myosin
- Prevents the muscles from pulling apart completely
What does troponin do?
Connects to tropomyosin
- Pulls tropomyosin away from the actin/myosin binding site when bound to Ca+
- Myosin head can bind to actin
Why can troponin not work in relaxed muscle?
No Ca2+ to bind to the troponin for it to pull the tropomyosin away and reveal actin/myosin binding sites
What occurs during muscle contraction?
EXCITATION-CONTRACTION COUPLING:
1) Action potential arrives - depolarisation of the membrane
2) Action potential propagates down down the T-tubules - activates VG Ca2+ ion channels in the sarcoplasmic
3) Voltage gated Ca2+ channels open
4) Ca2+ rapidly diffuses out of the SR down the concentration gradient into the SARCOPLASM
5) Ca2+ binds to toponin - conformational change
6) Troponin pulls tropomyosin from the myosin/actin binding
7) Myosin head sticks to the binding site on actin
8) If ATP/ADP available - cross bridge cyclic occurs and muscle actively shortens
Why is there a delay in the activation of the sarcolemma and muscle contraction?
Ca2+ channels needing to be open etc. (cascade)
What are the consequences of the sliding filaments?
Muscle contraction
What is muscle tension that the myocytes can develop?
Proportional to the no. of cross bridges
What is the no. of cross bridges that can form?
What does this mean?
Proportional to the sarcomere length
Means there is an OPTIMUM resting length for the maximum tension generation (as there is a point were there will be maximum no. of cross bridges forming)
What is the frank-stalin relationship?
The length-tension relationship
Describe the frank-stalin relationship graph
Short sarcomeres:
- Overlapping thin filaments
- LESS tension generated
- Action interfere with binding sites
- No actin-myosin binding
Optimum length:
- Absolute maximum no. of actin-myosin binding sites
Increase length past optimum:
- Actin and myosin are pulled apart
- Reduced area for cross bridge formation
Increase length too much:
- No binding at all
What is the optimum length of the sarcomere?
Where the MAXIMUM no. of binding sites
Where the MAXIMUM tension is generated
How do muscles constantly work at the optimum range?
Tendons and bones and angle of the joints
How can the frank-stalin relationship occur in heart muscle when the heart isn’t joined to any bones?
- If increase the venous return –> heart keeps expanding
- Sarcomere length increase
- Forced produced is less (more than optimum sarcomere length)
- More blood left in the heart (can’t expel blood properly)
- Heart is stretched more
- Go onto the descending part of the frank-stalin curve
What can happen if go on the descending curve of the frank-stalin in the cardiac muscle?
Heart faliure
As well as sarcomeres, what else contributes to tension curve?
Passive elastic structures
What is the ACTIVE force in the heart?
PASSIVE force?
Active force - contraction of the myocytes
Passive force - Elastic recoil
What happens when add the active force and passive force together?
Graph that keeps on INCREASING
What length is the sarcomere at maximum tension?
At maximum cross-bridges?
- 2 micro metres
2. 2 micro metres
How should the heart fill be to create a heart to generate sarcomeres in 2.2 micro metres?
What is this pressure called?
10-12mmHg filling pressure
Called the pre-systolic pressure
What is the presystolic pressure?
The pressure at rest when the blood fills the left ventricle
How is muscle contraction strength increase in skeletal muscle?
Recruit more motor units to increase muscle contraction
How is muscle contraction strength increase in cardiac muscle?
DON’T RECRUIT more muscle fibres
Instead, just CHANGE THE FORCE that each myocyte is able to produce
What is the force-velocity relationship?
Heavier the weight/load - the slower the rate of contraction
What is isotonic contraction?
Contraction of the muscle where the tension remains the SAME throughout contraction
What is the muscle in the vessels stretched by?
The pre-load (end diastolic volume)
What is the afterload?
Force at which the cardiac myocytes have to push against to eject blood:
- Arterial blood pressure
- Vascular tone
What is the relationship between shortening velocity and afterload?
Inverse relationship:
Increase afterload - decrease shortening velocity
What happens to the contraction strength if increase the pre-load?
STRONGER contraction (providing stay in the optimum range of the sarcomere)
When is a change in contractility shown?
When the output of the heart changes but the diastolic volume remains the same
When does contractility in the heart increase?
When more cross bridges from per stimulus (due to increase in Ca2+ per stimulus)
What does the contractility reflect?
The QUALATIVE state of the actin/myosin cross-bridges
What are changes in contractility called?
Positive (increase) or negative (decrease) IONOTROPIC effects
What are the changes in speed/rate of contraction called?
Chronotropic effects
What does noradrenaline release from the sympathetic nervous system cause?
Increase in MAXIMAL FORCE (ionotropic) and in Vmax (chronotropic - rate)
What increases the initial velocity of shortening?
Amount of noreadrenaline
Describe the frequency-force relationship?
Inter-beat duration (between beats) influences the FORCE of contraction:
- Positive ionotropic/chronotropic
- If increase the FREQUENCY (chronotropic) of stimulation (reduce inter-beat duration) INCREASE contractility (ionotropic)
Why does the increase in frequency of beats increase the force contraction?
Changs the Ca2+ availability within the sarcoplasm:
- Pumps in the SR have MAXIMUM RATE of which they work to remove Ca2+ from the sarcoplasm
- When they reach this rate - can’t increase any further
- If stimulate the muscle quickly - amount of Ca2+ in the sarcoplasm increase very quickly
- Accumulation of Ca2+ with each beat
- Ca+ bind to troponin - uncovering the actin/myosin binding site
