15-09-22 - Cardiac Contractility and the Events of the Cardiac Cycle Flashcards
Learning outcomes
• To explain how force is produced in cardiac muscle, how it differs from skeletal muscle and how it can be influenced by the extrinsic sympathetic nerves.
• To relate the timings of the electrical activity of the heart to the resulting mechanical events of the cardiac cycle.
• To interpret cardiac volume/pressure diagrams and state how they differ between the left and right sides of the heart.
What is the cardiac myocyte?
What is the function of these cells?
What do they consist of?
• The cardiac myocyte (also myocardiocytes) is the basic functional unit of the heart muscle
• These cells make up the heart muscle/cardiac muscle
• Cardiomyocytes are primarily involved in the contractile function of the heart that enables the pumping of blood around the body
• Cardiomyocytes consist of parallel bundles of myofibrils surround by sarcoplasmic reticulum (SR)
• Each myofibril is composed of sarcomeres connected in series at z-discs
What is excitation contraction coupling?
How fast is the cardiac action potential?
What are t-tubules?
What do triads consist of?
How is the action potential brought into the interior of the muscle fibre?
What happens to this change in membrane potential?
• Excitation contraction coupling is the linkage between excitation of the muscle fibre membrane (sarcolemma) and the onset of contraction
• The cardiac muscle action potential is 200ms
• T-tubules (transverse tubules) are invaginations of the cell membrane of muscle cells
• A triad consists of a transverse tubule (t-tubule) sandwiched between 2 terminal cisternae (enlarged areas of sarcoplasmic reticulum)
• Triads are specialised structures that allow the action potential to be delivered deep into the muscle fibre, where the change in membrane potential can be sensed and converted into a mechanical response
What do pacemaker cells undergo? What does this allow?
What is the resting potential of pacemaker cells like?
What is characteristic of pacemaker potentials?
What is the key event which leads to force generation in the heart muscle?
Describe the 3 steps that cause the contraction of the heart.
Describe the autonomic innervation of the cardiac muscle (parasympathetic and sympathetic), stating the neurotransmitter, action and innervation
• Pacemaker cells undergo automatic rhythmical depolarisation
• This allows pacemaker cells to set the rhythm of the cardiac tissue
• Pacemaker cells have an unstable resting potential
• Pacemaker potentials always depolarise to threshold
• The increase in intracellular calcium concentration from <10^-7M to >10^-5M is the key event which ultimately leads to force generation through interaction of actin and myosin filaments, which causes the contraction of the heart muscle
• 3 steps that cause the contraction of the heart:
1) Pacemaker cells initiate a depolarisation and generate an action potential
2) Electrical signal is propagated down the conduction pathway into the left ventricle
3) The electrical signal is converted into a mechanical response, which causes the contraction of the heart
• Autonomic innervation of the heart:
1) Parasympathetic:
• Neurotransmitter – acetylcholine
• Action – slows rate
• Innervation – localised to pacemakers
2) Sympathetic:
• Neurotransmitter – nor-adrenaline
• Action – increases rate and strength
• Innervation – diffuse
Describe the cardiac muscle action potential.
What occurs during the plateau?
When does muscle tension occur during the action potential in cardiac tissue?
• The cardiac muscle action potential has a rapid depolarisation followed by a plateau period, where we get an extension of the action potential prior to repolarisation
• During this plateau, we get an elevation in the intracellular calcium, which is the key event in force generation
• In cardiac muscle, there is onset of muscle tension during the action potential
What are the sources for calcium needed for contraction in cardiac muscle?
What % of Calcium needed for contraction enters through each source?
What is this process known as?
• In cardiac muscle, only approximately 10% of the required Ca2+ enters through the voltage gated L-type Ca2+ channels (DHP receptor protein channels) in the transverse tubular membrane
• The calcium acts as a ligand for ligand gated RYR channels, resulting in the RYR channels on the SR surface opening, and remaining 90% of calcium required for contraction entering into the cell
• This process is known as Ca2+ induced Ca2+ release (CICR) in cardiac muscle
Describe the 7 steps of the process of excitation contraction process in the cardiac muscle
- 7 steps of the process of excitation contraction process in the cardiac muscle
1) The cardiac action potential is generated on the surface of the cardiac muscle by the SA node cells and is delivered across cardiomyocytes via gap junctions connecting the cardiac cells together
2) The change in membrane potentials of cardiomyocytes is delivered deep into the muscle fibres by t-tubules, which are invaginations of the cardiac muscle cell membrane
3) This change in membrane potential will activate voltage-gated L-type calcium channels (DHP receptor channels, where the receptor sensed change in voltage) on the sarcolemma, but most L-type calcium channels are found on t-tubules
4) Calcium will flow into the cell and bind to the type 2 ryanodine receptors (RYR) on the SR membrane in a process called calcium induced calcium release.
5) Calcium will flow down its concentration gradient from the SR into the cytoplasm, where calcium can bind to the contractile machinery (troponin-c)
6) When calcium binds to troponin-c, this moves tropomyosin out of the way, which opens up the actin binding site on the sarcomere
7) Myosin globular heads can now form cross-bridges to these actin binding sites and initiate contraction of the cardiomyocyte
What is SERCA?
What activates SERCA?
How does skeletal muscle relaxation occur?
How many molecules of Calcium are transported per molecule of ATP hydrolysed?
What does the cytoplasmic concentration of Calcium drop to?
What is calsequestrin?
What is its role? What is its molecular weight?
How many calcium ions can it bind per molecule?
• SERCA is the Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (Ca2+ ATPase)
• SERCA in the SR membrane is activated by the increase in intracellular calcium concentration during the process of contraction
• Skeletal muscle relaxation occurs when calcium is pulled back into the SR stores via SERCA through active transport, as the calcium goes against its concentration gradient
• 2 calcium ions are actively transported from the cytoplasm to the SR per molecule of ATP hydrolysed
• The cytoplasmic concentration of calcium drops back to <-10^-7M (relaxation)
• Calsequestrin is a calcium buffering protein found in the SR
• Calsequesterin binds to free calcium in order to reduce the free calcium concentration, and reduce the concentration gradient for calcium moving from the cytoplasm back into the SR
• It has a molecule weight of 44000
• It can bind 43 Ca2+ ions per molecule
Describe the 5 steps of the process of relaxation after contraction in the cardiac muscle
• 5 steps of the process of relaxation after contraction in the cardiac muscle
1) After contraction, the calcium is pumped back into the SR stores against its concentration gradient via SERCA pumps
2) Calsequestrin will mop up as much free calcium as it can to try and reduce the concentration gradient of calcium (still an active process requiring ATP)
3) Calcium is also extruded from the cell via Ca2+, Na+ exchanger. 3 sodium ions echanged per calcium ion
4) Na+ concentration has to be maintained by the NaK ATPase in order to avoid an unwanted action ptoential from being generated
5) Relaxation occurs when the cytoplasmic calcium concnetration goes from >10^-5M to <10^-7M
How much bigger in size and volume are cardiac t-tubules compared to skeletal t-tubules?
What do cardiac t-tubules sequester?
Why can’t resting heart rates cause maximal contractile force?
What happens to calcium release when the resting heart rate is increased?
How does this affect force of contraction?
What is contractility?
How can calcium storage for relaxation affect the refractory period of the heart?
- Cardiac t-tubules are 5x greater in diameter and have 25x more volume than skeletal t-tubules
- Cardiac t-tubule mucopolysaccharides sequester Ca2+
- At resting heart rates, there is not enough calcium released into the cell from the SR to cause maximal contractile force
- When the resting heart rate is increased, this will lead to more calcium being released, which will bind to more troponin, which will move tropomyosin and reveal more actin binding sites for myosin globular heads to form cross bridges with
- This will lead to greater force of contraction
- Contractility is the strength of contraction of the heart
- We can favour calcium being extruded from the cell when relaxing the heart, meaning less calcium will be available for release during contraction
- This will result in a lower refractory period (time when heart can’t generate another AP – usually about 250ms)
What does chronotropic effect mean?
What does inotropic mean?
What does preload mean?
What chronotropic and inotropic effect does the ANS have on heart rate?
Where can autonomic (sympathetic and parasympathetic be found on the heart?
What stimulation does the ANS have on pacemaker activity?
Through what processes do they achieve this?
- Chronotropic effects are those that change the heart rate
- Inotropic effects are those that affect contractility
- Preload refers to how much blood is in the ventricles prior to the ventricle contracting / Preload is the initial stretching of the cardiac myocytes prior to contraction (force comes from volume of blood in ventricle)
- How the ANS affects the nervous system stimulation on pacemaker activity
- Sympathetic innervation
- Positive chronotropic effect
- Positive inotropic effect
- Capable of modifying the intrinsic pacemaker potential in the SA node and conduction through the AV node
- Only sympathetic innervation can control contractile forces affecting the entire heart
- Noradrenaline acts on β1 receptors to increase cAMP production which can activate protein kinase, which can phosphorylate and modify the activity of pumps
- Beta-1 receptors, along with beta-2, alpha-1, and alpha-2 receptors, are adrenergic receptors primarily responsible for signalling in the sympathetic nervous system.
- This increases the rate of SAN phase 1 depolarisation through increasing gCa2+ and gNa+ via F-type Na+ channels (funny channels)
- Sympathetic enhance Ca2+ influx, and promotes the storage and release of Ca2+ from sarcoplasmic stores
- Therefore, this will lead to an increase in contractility and speed of relaxation
- These changes increase the heart rate
- Parasympathetic
- Negative chronotropic effect
- There is no negative inotropic effect on the heart, except in pathological circumstances, there is only removal of sympathetic innervation to return to resting levels, otherwise the heart would fail
- Capable of modifying the intrinsic pacemaker potential in the SA node and conduction through the AV node
- Vagi (parasympathetic control) innervates only nodal tissue
- Acetylcholine on M2 receptors, which decrease Camp production
- The M2 muscarinic receptors are located in the heart, where they act to slow the heart
- Parasympathetic innervation reduces the rate of phase 1 depolarisation
- It does this by hyperpolarising the membrane potential to a lower starting potential
- This is done by increasing the extent and duration of opening of K+ channels, therefore increasing the gK+
- These changes reduce heart rate
What do cardiac twitches involve?
Can cardiac contractions summate?
Why is this?
What is the refractory period?
Why is the refractory period important?
How can the refractory period be affected when cardiac cells relax?
How can the heart contract during an action potential?
What is the absolute refractory period and period of contraction of skeletal muscle and cardiac muscle?
What 2 other periods are we concerned about in cardiac action potentials?
Can action potentials be generated during these periods?
What happens if action potentials are generated during these periods?
- Cardiac twitches involve all fibres of the myocardium (muscular tissue of the heart)
- We can not significantly summate contractions of the cardiac muscle
- This is because of the refractory period
- The refractory period is a period we can’t generate another action potential due to inactivation of Na+ channels
- The refractory period is important as it allows the heart to relax and fill with blood
- By extruding more calcium from the cardiac cells instead of taking it back into the SR during relaxation, this will cause less calcium to be released during the next action potential, which will cause the refractory period to be lower
- The heart can contract during an action potential due to the heart cells being electrically connected and forming a functional syncytium
- Skeletal muscle
- Absolute refractory period – 1-2ms
- Period of contraction – 20-100ms
- Cardiac muscle
- Absolute refractory period (ARP) – 245ms (no action potential can be generated)
- Relative refractory period (RRP) – Where a stronger than normal signal can induce an action potential
- Period of supranormal excitability (SNP) – Where a lower-than-normal stimulation could cause action potential
- Period of contraction – 250ms
- If action potentials are generated at the RRP or SNP, the heart will contract with less force due to incomplete filling and reset of the heart
- This can lead to heart failure
Diagram of pressure in chambers of the left side of the heart during systole and diastole.
How would these pressures differ for a diagram of the right side of the heart?
Describe when systole and diastole starts through the opening and closure of valves on the left side of the heart
What are the 3 heart sounds made by during this cycle?
- If this diagram represented the right side of the heart, the pressures would be lower, as less pressure is required to pump blood to the lungs than to the whole body
- When systole and diastole start through the opening and closure of valves on the left side of the heart and when heart sounds occur during this cycle:
1) Systole starts and diastole ends with the closure of the mitral valve, which produces the 1st heart sound
2) Shortly after this, the aortic valve opens and the left ventricle pumps blood into the aorta
3) Systole ends and diastole starts with the closure of the aortic valve, which produces the 2nd heart sound
4) Shortly after this, the mitral valve opens, which allows passing filling of the ventricle, which forms the 3rd heart sound
Describe what happens to ventricular volume at points 1, 2, and 3 on the diagram
• Point 1 on diagram
• Blood is rapidly pumped out of the ventricle during systole
• Some blood is left in the ventricle to prevent ventricles from sticking
• Point 2
• Av valve opens and blood passively goes from the atria to the ventricles
• Point 3
• Blood is actively pumped out of the atria to the ventricles
Describe what happens to ventricular pressure at points on the diagram.
How does exercise affect this graph?
- Point 1 on the diagram
- More pressure in the ventricle than the atria causes the AV valve to close
- Gives the first heart sound
- Point 2
- Ventricle contracts and presses against the blood in the ventricle
- Point 3
- There is a change in pressure with no change in ventricle volume because the AV and aortic valve are closed
- This causes the ventricle to squeeze the blood, leading to an increase in pressure
- Point 4
- When the pressure in the ventricle is greater than the pressure in the aorta, the aortic valve opens
- This allows blood to be pumped into the aorta
- Point 5
- When the ventricle relaxes, the pressure inside the aorta becomes greater than that in the ventricle
- This causes the aortic valve to close
- Point 6
- When the aortic valve snaps shut, there is a rebound in aortic pressure
- During exercise, there is greater pressure, but it resolves faster
What is end systolic volume (ESV)?
What is end diastolic volume (EDV)?
What is stroke volume (SV)?
What is cardiac output (CO)?
• End systolic volume (ESV) – Volume in the ventricle at the end of systole
• End diastolic volume (EDV) – Volume in the ventricle at the end of diastole
• Stroke volume (SV) – (formula = EDV-ESV) Quantity of blood expelled per beat (L)
• Cardiac output (CO) – (formula = SV X HR) Volume of blood pumped by the heart (L/min)
• Pressure loop diagram without time:
