1.1.1
Cardiac action potential – contractile cells
The cardiac action potential differs significantly depending on the function of the cardiac myocyte (i.e. excitatory/pacemaker or contractile). The action potential of contractile cardiac myocytes has 5 phases characterized by a stable resting membrane potential and a prolonged plateau phase.
Phase 0 – rapid depolarization as membrane permeability to potassium decreases and fast sodium channels open.
Phase 1 – early rapid repolarization as sodium permeability decreases.
Phase 2 – plateau phase. A continued influx of calcium through L-type (long opening, voltage-gated) calcium channels maintains depolarization for approximately 300 ms.
Phase 3 – rapid repolarization due to inactivation of calcium channels and ongoing efflux of potassium.
Phase 4 – restoration of ionic concentrations, thereby restoring the resting membrane potential of approximately –90 mV.
For the majority of the action potential, contractile myocytes demonstrate an absolute refractory period (beginning of phase 0 until close to end of phase 2). During this time no stimulus, regardless of the magnitude, can incite further depolarization. A relative refractory period exists during phase 3. A supramaximal stimulus during this period will result in an action potential with a slower rate of depolarization and smaller amplitude, producing a weaker contraction.
Anti-arrhythmic drugs and the myocardial action potential
Anti-arrhythmic drugs (see Section 1.1.22 – Vaughan–Williams classification) that alter ion movement are used to alter action potentials to prevent or terminate arrhythmias.
In contractile cells, sodium channel blockers (Vaughan–Williams Class 1) reduce the slope of phase 0 and the magnitude of depolarization. They also prolong the refractory periods by delaying the reactivation of sodium channels.
Potassium channel blockers (Vaughan–Williams Class 3) delay phase 3 repolarization. This lengthens the duration of the action potential and the refractory periods.
1.1.2
Cardiac action potential – pacemaker cells
The pacemaker potential is seen in cells of the cardiac excitatory system, namely the sinoatrial (SA) and atrioventricular (AV) nodes. Action potentials of cardiac pacemaker myocytes have 3 phases (named out of numerical order to coincide with contractile myocyte action potentials) and are characterized by automaticity, due to an unstable phase 4, and a lack of plateau phase.
Phase 4 – spontaneous depolarization. Sodium moves into myocytes via ‘funny’ voltage-gated channels that open when the cell membrane potential becomes more negative, immediately after the end of the previous action potential. Calcium also enters the cell via T-type channels (T for transient).
Phase 0 – rapid depolarization occurs once the threshold potential (approximately −40 mV) is reached. L-type calcium channels open and calcium enters the cell.
Phase 3 – repolarization occurs as potassium permeability increases, resulting in potassium efflux.
Compared to contractile myocytes, pacemaker myocyte action potentials:
are slow response
have a less negative phase 4 membrane potential
have a less negative threshold potential
have a less steep slope of rapid depolarization (phase 0).
Regulation by the autonomic nervous system
The cardiac excitatory system demonstrates inherent pacemaker activity. The rate of depolarization and duration of action potential are influenced by the autonomic nervous system. In the denervated heart, the SA node depolarizes at a rate of 100 bpm. At rest, parasympathetic activity dominates and reduces SA nodal depolarization. Parasympathetic activation leads to an increase in potassium efflux while reducing sodium and calcium influx. These alterations in ionic conductance result in a more negative phase 4 membrane potential, a decrease in the slope of phase 4 and, overall, an increase in the time to reach the threshold potential. Conversely, sympathetic activation increases the rate of pacemaker depolarization by reducing potassium efflux and increasing sodium and calcium influx.
1.1.3
Cardiac action potential – variation in pacemaker potential
The pacemaker potential is seen in cells in the SA and AV nodes. It is a slow positive increase from the resting potential that occurs at the end of one action potential and before the start of the next. The pacemaker action potential differs from those seen in other cardiac cells because it lacks phases 1 and 2 and has an unstable resting potential. This unstable resting potential allows for spontaneous depolarization and gives the heart its autorhythmicity. It is the rate of change, or gradient, of the resting potential that determines the onset of the next action potential and therefore the discharge rate. The characteristics of the pacemaker potential are predominantly under the control of the autonomic nervous system.
An increase in the gradient of the slope of phase 4 will reduce the amount of time taken for the cell to reach threshold potential, causing depolarization to occur more rapidly. This occurs with sympathetic stimulation (red trace) via β1 adrenoreceptors which results in an increase in cyclic-AMP levels, allowing the opening of calcium channels and thereby increasing the discharge rate of the cell.
Conversely, a decrease in the slope of phase 4 will increase the time taken to reach threshold potential and depolarization, causing a reduced discharge rate. This occurs with parasympathetic stimulation (blue trace). The vagus nerve acts to slow the discharge rate by hyperpolarizing the cell membrane through increased permeability to potassium. The membrane potential is therefore more negative so will take longer to reach threshold potential and to discharge.
1.1.4
Cardiac cycle
The diagram depicts events that occur during one cardiac cycle. It is a graph of pressure against time and includes pressure waveforms for the left ventricle, aorta and central venous pressure (CVP), with the electrocardiogram (ECG) and heart sound timings superimposed.
There are five phases.
Phase 1 (A). Atrial contraction – ‘P’ wave of the ECG and ‘a’ wave of the CVP trace. Atrial contraction (or ‘atrial kick’) contributes to about 30% of ventricular filling.
Phase 2 (B). Ventricular isovolumetric contraction (IVolC) – marks the onset of systole and coincides