Week 3- Heart as an electrical pump Flashcards
Explain the structure of cardiac myocytes and how they function as a syncytium
Cardiac myocytes are shorter, branched and interconnected end to end by intercalated discs. These intercalated disks connect the ends of myocytes physically via desmosomes and gap junctions which link cells electrically. Cardiac muscle acts as a mechanical and electrical synctium of coupled cells. When the SAN depolarises, the AP is propagated through cardiac myocytes which are electrically coupled via gap junctions producing a low threshold all or nothing response with rapid propagation of electrical activity.
Describe the internal structure of a cardiac myocyte
Internally cardiac myocytes are composed of myofibrils containing myofilaments. A myofibril is an end to end chain of sarcomeres- which consist of smaller interdigitating filaments called myofilaments.
Myofilaments contain both thick and thin filaments. Thick filaments are composed primarily of myosin and thin filaments primarily of actin.
The interdigitation of actin and myosin forms the repeating microanatomical unit called the sarcomere which extends from one Z line ) intercalated disc) to another. The sliding of actin over myosin is what shortens the sarcomere and leads to muscle shortening and contraction.
The dark bands represent areas of myosin and actin overlapping. The light regions are where only actin overlaps.
What is excitation- contraction coupling?
Describe the process and how it results in muscle contraction
The process by which electrical excitation of the surface membrane triggers an increase in IC Ca2+ is known as excitation-contraction coupling. Action potentials originating at the surface membrane of cardiac muscle propagates into the interior of the cell via T tubules which are invaginations of the sarcolemma. These T tubules project down into the cell and contact the sarcoplasmic reticulum. The propagation of an AP from the SAN depolarises voltage gated Ca2+ channels on the sarcolemma T tubule membrane. These are mechanically coupled to Ca2+ channels on the sarcoplasmic reticulum- opening them. [Ca2+]i rises, binds to troponin C - moves tropomyosin from binding site for myosin head on actin.
Describe the process of muscle contraction once Ca2+ has risen
Ca2+ binds to troponin C on the actin filament
Binding causes tropomyosin to move, reveals the actin binding site for myosin head
ATP is bound and hydrolysed to ADP by ATPase in myosin head, provides the energy for myosin head cycling. Conformational changes in myosin results in movement of myosin heads along actin filaments.
This movement results in muscle fibre shortening .
Describe the role of calcium in cardiac contraction
How does it allow cross bridge formation?
What does the EC ca2+ concentration control?
How is Ca2+ removed during relaxation?
Calcium facilitates the process of contraction by binding to the troponin C molecule in the troponin complex. This moves troponin i (inhibitory) away from actin/tropomyosin filament, permits tropomyosin to move and allows the myosin head to bind the actin filament forming a cross bridge.
The concentration of Ca2+ in the EC fluid determines the strength of cardiac muscle contraction.
The higher the concentration, the greater the number of activated troponin molecules.
At the end of the action potential Ca2+ flow is reversed. IC Ca2+ pump on the sarcoplasmic reticulum pumps Ca2+ back into the SR and Ca2+ is removed from the cell via a Ca2+/Mg2+ ATPase. Lowered Ca2+ concentration stops actin myosin interaction and relaxation ensues.
Describe the conduction system in the heart
The cardiac action potential originates in the SA node located in the right atrium. These cells spontaneously depolarise at a rate of 60-100 times at rest. As cardiac cells are electrically coupled via gap junctions the AP propagates cell to cell from the R atrium the the L.
Signal then arrives at the atrioventricular (AV) node. This impulse does not spread directly to the ventricles due to the presence of an atrioventricular ring. The impulse then travels down the His-Purkinje system, which splits into R and L bundles of His before becoming the purkinje fibres at the apex of the heart. This purkinje fibres curve back up into the ventricles which contract in a coordinated manner.
What node is the primary pacemaker? What would happen if this node failed to function?
The SA node is the primary pacemaker; however if it failed to generate AP’s another focus would take over.
The other focus is normally within the atrium, or the AV node, however bundle of His can also take over. Generally the lower in the conduction system the slower the generated AP.
Sino atrial cells are modified muscle cells characterised by:
1) ?
2) ?
Pacemaker activity is ____________ generated.
The SA node cells are modified muscle cells characterised by:
1) No true resting potential
2) the generation of regular and spontaneous AP’s.
Pacemaker activity is spontaneously generated.
Pacemaker activity can be modified significantly by:
1)
2)
3)
4)
5)
6)
1) autonomic nervous system
2) hormones
3) ions
4) drugs
5) ischaemia
6) hypoxia
Describe the pacemaker potential - where does this primarily act?
What phases are there?
What ions produce these phases?
SA node is the primary pacemaker of the heart having no true resting membrane potential and generating regular, spontaneous action potentials. The action potential generated in the SA node is very similar to that of the AV node.
Unlike non pacemaker action potentials in the heart, depolarisation of the pacemaker cells is via slow Ca2+ currents rather than fast Na+ currents.
SA node AP divided into three phases:
1) spontaneous depolarisation- phase 4
2) depolarisation - phase 0
3) repolarisation -phase 3
1) Phase 4- spontaneous depolarisation due to slow inward movement of Na+ via funny current (when membrane potential very negative around -60mV). Get spontaneous depolarisation and opening of transient Ca2+ channels. As ca2+ moves down its conc gradient membrane potential reaches around -40mv.
2) Phase 0- Depolarisation happens when threshold is reached, get opening of voltage gated L type Ca2+ channels. Funny current and T type Ca2+ channels close, Ca2+ via L type.
3) repolarisation occurs as K+ channels open, generates outward directed K+ currents that hyperpolarise the cell. L type Ca2+ channels become inactivated and close.
After repolarisation the Na/K ATPase corrects IC concentrations of K+ and Na+.
Describe the non pacemaker Action potential - what parts of the heart does this act in?
What phases are there?
What ion movements produce these phases of the AP?
What is an effective refractory period?
Non pacemaker potentials act in the atria, ventricles and purkinje fibres of the heart. These action potentials undergo rapid depolarisation mainly caused by fast influx of Na+.
Non pacemaker cells have a true resting membrane potential of around -90mV, close to equilibrium potential for K+. Phase 4 = equilibrium potential where open K+ channels keep the membrane potential negative.
When an AP arrives from an adjacent cell, the membrane potential is depolarised to threshold of around -70mV. Leads to phase 0 rapid depolarisation caused by Na+ influx and K+ channel closure.
Phase 1 represents an initial repolarisation caused by transient outward K+ current that is short lived.
Phase 2 plateau phase- caused by the influx of Ca2+ via L type channels which open when the membrane potential reaches around -40mV. Ca2+ entry is pivotal in allowing muscular contraction. Plateau phase prolongs AP important for proper contraction of the heart.
Phase 3 repolarisation phase occurs when these L type Ca2+ channels close and K+ channels reopen, eflux of K+ repolarises the cell.
After repolarisation the Na/K pump returns Na+ to the ECF and K+ IC.
After an AP has been initated there is then an effective refractory period where stimulation of the cell by another AP will not produce cell depolarisation. This is because Na+ channels remain inactivated following channel closure after phase 1.
What is the difference in the refractory period of cardiac vs skeletal muscle?
Why is this important?
The refractory period in cardiac muscle is relatively longer than that of skeletal muscle. During phases 0, 1 ,2, and part of phase 3 the Na+ channels that are responsible for fast depolarisation are in an inactivated state and cannot reopen even if the cell is further stimulated.
The effective refractory period acts as a protective mechanism in the heart, preventing multiple AP’s from occuring at once which allows the heart to adequately fill with blood for ejection and limiting the number of contractions (prevents tetanus). In skeletal muscle this refractory period is short, meaning multiple AP’s can cause repeating contractions- tetanic state.
explain the propagation of action potentials in the heart at the cellular level
1) Change in membrane potential and ion movements
2) How it spreads to adjacent myocytes
3) why does it spread in one direction
1) change in potential difference across the cell surface from -90mV to positive potential (+20mV at full depolarisation)- Rapid deplarisation phase caused by fast influx of Na+ via voltage gated channels. Reaches a plateua phase (opening of transient K+ channel initates repolarisation but opening of L type Ca2+ channels to maintain positive potential and allows excitation- contraction coupling).
2) Spread of depolarisation in adjacent myocytes by diffusion of positive Na+ ions via gap junctions inbetween cardiomyocytes. Adajcent mycoyte reaches threshold and AP initatiated.
3) Unidirectional: AP moves in direction opposite to refractory zone. After cardiomyocyte has finished AP it immediately enters refractory period and cannot be stimualted by another AP. (Sodium channels are inactivated.)
What two myocardial syncytia are there?
What allows the spread of electrical activity from one myocardial synctia to the other?
What does this structure do and what does this allow for?
There is atrial and ventricular syncytia within the heart.
The two synctia are separated by the fibrous skeleton of the heart and electrical conduction passes from one to the other via the AVN.
The AVN induces a delay which is vital to allow proper filling of the ventricles and contraction of the atria to push sufficient blood into the ventricle.
Excitation : The _______ __________ originates in _________ _______. Passes along membranes of _________ __________.
Contraction: ___________ _____________ initiates the release of ________ into the myocyte __________.
Coupling: _________ facilitates the process of contraction.
Excitation: Action potential originates in pacemaker cells. Passes along the membranes of myocyte syncitium.
Contraction: Membrane depolarisation initiates the release of calcium into the mycoyte cytoplasm.
Coupling: Calcium facilitates the process of contraction.
Describe the cardiac cycle during diastole explaining both atrial/ventricular volume/ pressure changes, aortic pressure changes and relating to the ECG and JVP waveform.
Diastole:
1) ventricular pressure falls below atrial pressure
2) allows opening of mitral/ tricuspic valves and rapid filling phase with passive movement of blood from atria to ventricles
3) Corresponding increase in ventricular volume
4) rapid filling phase slows and reaches plateau called diastasis
5) P wave on ECG occurs at the end of diastasis
6) atrial contaction causes slight increase in intratrial pressure and intraventricular pressure and volume.
Explain the systolic phase of the cardiac cycle- reference again atrial/ventricular pressure and volume, aortic pressure, any valve opening/closure and relate to ECG and JVP pressure waveform
Systole: After diastole finishes with atrial contraction and corresponding increase in ventricular volume:
1) QRS complex on ECG shows depolarisation of the ventricles
2) Isovolumic contraction: Ventricles contract, increase in pressure above that of atria- forces mitral/tricuspid valves shut. The aortic/ pulmonary valves also closed at this time. Contraction against closed valves leads to sharp increase in pressure. Shows as a C wave on the JVP trace- represents bulging of tricuspid into right atrium during systole.
3) Ventricular pressure exceeds that of aorta, forces the aortic (or on R side pulmonary) valves open. Corresponding drop in ventricular volume during ejection.
4) Pressure in ventricle rises closely followed by increase in pressure in aorta.
5) ventricular contraction finishes and pressure starts to fall. Corresponds to T wave in ECG as ventricles repolarise.
6) Aortic (and pulmonary valves) shut as pressure in ventricle falls below aortic pressure- creates dicrotic notch in arterial waveform.
7) isovolumic relaxation occurs as ventricles relax and both the AV valves and aortic/ pulmonary valves are closed. Pressure drops dramatically until pressure of atria overcomes ventricular and filling starts again.
Explain the JVP waveform
a wave- atrial contraction
c wave- bulging of the tricuspid back into right atrium during ventricular systole
x descent- atrial relaxation
V wave- atrial venous filling at the end of ventricular systole
Y descent- opening of tricuspid valve
Describe the points in the ventricular volume/pressure loop
1) point 1 represents mitral valve closure at the end of diastole. The ventricle has reached end diastolic volume and starts to contract against a closed mitral valve and closed aortic valve. Leads to sharp increase in pressure but no change in volume.
2) The pressure in the ventricle excees that of aorta and forces the aortic valve open. Initates ejection phase where the volume of the ventricle starts to fall with ejection of blood but pressure continues to rise with contraction until it reaches its peak systolic pressure.
3) Fall of pressure after the peak systolic pressure, aortic pressure exceeds ventricular leading to closure of aortic valve. Pressure in the ventricle declines rapidly during isovolumic relaxation where the walls are relaxing and all valves are shut. End systolic volume contained within the ventricles
4) pressure in ventricle falls below atrial, mitral valve opens and the filling phase begins. Volume of ventricles increases during rapid filling phase, pressure slowly increases as ventricles finish relaxing and start filling.
Difference between two vertical lines (end diastolic volume and end systolic volume) is the stroke volume.
