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

• h