How does the structure of the heart allow coordination conduction of electrical signals?
Cardiac muscle cells are uninucleate, rich in mitochondria and contain contractile actin and myosin fibres (striated).
Fibres may branch at either end and connect with the next cell in series through intercalated discs. Membranes of adjacent cells are linked by desmosomes and transmembrane channels form gap junctions which connect the cytoplasm of cells.
This provides electrical continuity from cell to cell, allowing easy transmission of action potentials. The heart therefore behaves as a syncitium, with rapid conduction of electrical signals leading to well coordinated contraction.
What is the resting membrane potential of cardiac muscle?
Why is the prolonged refractory period in cardiac action potentials important?
It ensures that relaxation occurs before further contraction can be generated (prevents summation or tetanus at high frequencies of stimulation).
Cardiac cells are refractory to stimulation for the entire duration of the action potential. Contraction and relaxation are complete within this time. Therefore refractory period also prevents against pump failure caused by sustained contraction.
Describe the mechanism of the cardiac action potential.
Depolarisation opens Na+ channels which produces a fast inward current. If the threshold value is reached, this causes further depolarisation and more Na+ channels open producing the rapid depolarisation phase (+20mV).
Na+ channels become inactivaed, and K+ channels open, causing a transient repolarisation. Depolarisation also opens L-type (slow) Ca2+ channels and the Ca2+ influx produces a plateau in the action potential via Ca2+ release from the SR.
Delayed inward rectifyer K+ channels open increasing K+ leaving the cell which repolarises the membrane. Ca2+ channels close and Ca2+ is removed from the cytoplasm.
Where is the SA node located?
Right wall of the atrium, posterior, close to the SVC
Where is the AV node located?
Lower half of the right atrium, on the atrial septum
Describe the conducting pathways in the heart
Cardiac action potentials originate in the SA node and are conducted through the atrial muscle fibres via gap junctions at 0.3 ms-1. This produces coordinated atrial contraction which forces blood into the ventricles.
Conduction through the AV node is slower (0.05ms-1). which delays transmission of the action potential to the ventricle. This ensures ventricular contraction will not begin until atrial contraction is complete.
Action potentials are conducted from the atria to the ventricles by the bundles of His which divide into left and right bundle branches that travel down the interventricular septum to the apex of the heart where they form Purkinje fibres that branch into the ventricular muscle. Conduction is rapid, which promotes synchronised ventricular contraction.
What is autorhymicity?
The abiliity to spontaneously fire action potentials in a regular pattern without the need for nervous input
How is intracellular calcium removed following a cardiac action potential?
Ca-ATPase on the plasma membane and SR
How is the pacemaker potential generated?
Pacemaker cells have ion channels that allow slow inward currents to gradually depolarise the cell.
cAMP-gated Na+ channels and T-type Ca2+ channels open causing depolarisation of the cell. The efflux of K+ is also reduced (controlled by cAMP) until the threshold is reached.
L-type Ca2+ channels open causing rapid depolarisation and an action potential is fired.Inactivation of Ca2+ channels allows repolarisation, aided by K+ channels opening.
The slope of the pacemaker potential determines the rate the SA node fires (sinus rhythm)
How does Noradrenaline produce positive chronotropic effects on the heart?
Noradrenaline binds to beta-adrenergic receptors, which are coupled to Gs. This stimulates adenylate cyclase and cAMP is increased.
cAMP regulates the Na+ channels in pacemaker cells, Na+ channels open and the cells are depolarised more rapidly.
An increase in firing at the SA node increases the rate of contraction.
How does Ach produce negative chronotropic effects in the heart?
Ach binds to M2 receptors in the heart which is coupled to Gi. This inhibits adenylate cyclase, reducing levels of cAMP which closes Na+ channels and causes K+ channels to open. K+ leaves the cell and it takes longer for the cell to become depolarised.
Class 1 anti-arrhythmic drugs
Block Na+ channels
1a: Block open channels. Delay depoarisation. Lengthens action potential e.g. quinidine
1b: Blocks Na+ channels in actively depolarising cells. Action potential is shortened. e.g. lignocaine
1c: Slow depoarisation and conduction speed. No change in duration of the action potential e.g. flecainide
Class 3 anti-arrhythmic drugs
Block K+ channels.
Delay repolarisation, action potential prolonged
Class 2 anti-arrhythmics
Act on SA node to block the pacemaker potential. Slows the heart rate.
Also reduce force of contractions by reducing [Ca]i
i.e. Used in atrial fibrillation
e.g. bisoprolol, propanolol
Class 4 anti-arrhythmic drugs
Block Ca2+ channels.
Myocytes: Reduce amplitude of the action potential and shorten the plateau phase. Force of contraction reduced (negatively inotropic)
Pacemaker cells: reduces rate of firing
Action of cardiac glycosides e.g. digoxin
Blocks the Na+/K+-ATPase.
Results in increased intracellular Na+
Ca2+ exchanged for Na+ via exchanger
Less Ca2+ is removed from the cell because the exchanger is inhibited by the concentration gradient
This increases contraction
Action of atropine on the heart
Speeds up the heart rate
Blocks muscarinic Ach receptors in the SA and AV node. Reduces parasympathetic effects, so the heart beats faster.
side effects: dry mouth, urinary retention, dilated pupils
What is the effect of decreased serum K+ levels on the heart?
Low extracellular K+ alters the electrochemical gradient so more K+ leaves the cell. Myocytes become hyperpolarised, therefore more stimulation is required to reacht he threshold and cardiac excitation is reduced.
What effect does an increase in serum Ca2+ levels have on the heart?
Hypercalemia can cause arrhytmias and cardiac arrest because Ca+ causes contraction of the myocytes. Cardiac arrest occurs in systole with the heart in full contraction
What effect does a decrease in serum Ca2+ levels have on the heart?
Reduction in plasma calcium causes a reduction in cardiac contraction, and reduced the intracellular Ca2+ stores.
Why does cooling the heart slow it down?
Pacemaker cells are sensitive to temperature.
Heart rate increases when there is an increase in body temperature, and is reduced when cooled.
Describe the ECG waveform and how is related to the different phases of contraction and relaxation of the heart
P wave: Atrial depolariation
PR interval: atrioventricular conduction (spread through the bundles of HIs to Purkinje fibres)
QRS complex: ventricular depolarisation (Q: interventricular septum, R: main mass of ventricle, S: apex and base of the heart)
QT interval: ventricular depolarisation and repolarisation (varies with heart rate)
T: ventricular repolarisation.
First degree heart block
Prolonged PR itnerval (>0.12s)
Wave of depolarisation from the SA node is conducted to the ventricles but there is a delay.
Can indicate coronary artery disease, rheumatic carditis, electrolyte disturbances.
Second degree heart block
Excitation fails to pass through the AV node or bundles of His
Mobitz type 2 heart block
Most beats have a constant PR interval, but there is an occasional dropped QRS complex (atria contract but ventricles don't)
Wenkeback heart block
Progressive lengthening of the PR interval until a QRS complex is dropped.
The next conducted beat has a shorter PR interval but then the cycle repeats.
Fixed ratio heart block
There are a consistent number of P waves for every QRS complex. (2:1 or 3:1)
Caused by alternate conducted and non-conducted atrial beats. Increases the ratio of P waves to QRS complexes.
[P wave may appear as a distortion of the T wave]
Third degree heart block
P waves and QRS complexes are independent of each other.
Atrial contraction is normal but there is no conduction to the ventricles. Ventricles are excited by a slow escape rhythm from a ventricular focus (30bpm)
May occur in patients with acute MI, or due to fibrosis around the bundle of His.
Right bundle branch block
No conduction to the right bundle beanch but the septum is depolarised on the left. It takes longer than normal for excitation to reach the right ventricle and it depolarises after the left. This results in a widened QRS complex.
An RSR' pattern is seen in V1 and a QRS complex with a deep wide S wave is seen in V6/lead I
ILeft bundle branch block
Conduction down the left bundle branch fails and the septum is depolarised from right to left, and the left ventricle depolarises after the right.
This produces a small Q wave in V1 (W pattern) and an R wve in V6 (M pattern). The QRS complexes are wider.
T waves are inverted.
What is the effect of increased serum K+ levels on the heart?
An increase in K+ levels (above 5mM) increases the cardiac excitation as the membrane potential of the myocytes is closer to threshold (more K+ ions enter the cell to balance the electrochemical gradient).
This can produce arrhythmias and may lead to ventricular fibrillation.
If the K+ levels increase to 7mM causes heart block because the VG-Na+ channels become inactivated because the cells are maintained near threshold, and are therefore non-excitable.
Causes of disturbed cardiac rhythm
delayed after-depolarisation: caused by raised [Ca2+]i which triggers an inward current.
re-entry: resulting from partial conduction block, parts of the myocardium remain depolarised due to disease. This disturbs the normal pattern of conduction and permits continuous circulation of the impulse to occur.
Ectopic pacemaker activity: usually encouraged by sympathetic activity
heart block: results from disease in the conducting system (particularly AV node).