Cardiac action potential

Cardiac tissues exhibit two types of action potentials depending on their function. The atria, ventricles, and Purkinje fibres have action potentials with fast depolarization and plateau phases. The pacemaker cells of the SA node and AV node have action potentials with a slower rate of depolarization and absence of the plateau phase. The resting membrane potential of cardiac cells is determined mainly by potassium ions. The atria, ventricles and Purkinje fibres have a resting membrane potential about -85 mv while the SA node start depolarizing when they reach a membrane potential of -65 mv.

1. Action potential of the atria, ventricles, and Purkinje cells: It is characterized by 5 phases - 0 to 4, long refractory periods, stable resting membrane potential, and a plateau phase of the action potential. Phase 0, also called rapid depolarization or upstroke of the action potential, is caused by the opening of the activation gates of the sodium channels. This causes sodium influx. Depolarization also causes the slow inactivation gate of the sodium channel to close. This is followed by Phase 1, or initial repolarization, which is due to two factors - the closing of the inactivation gates of the fast sodium channel and the opening of potassium channels. Potassium will move out of the cell while sodium influx will reduce. Phase 2 is also called the plateau phase. Opening of L-type (long-lasting) calcium channels and slow influx of calcium, along with continued potassium efflux through the open potassium channels, leads to the plateau phase. This is a critical phase as calcium influx leads to calcium-induced calcium release from the sarcoplasmic reticulum and excitation-contraction coupling causing myocardial contraction, i.e.systole. Phase 3 or repolarization is caused due to two factors - reduced calcium influx than before and increased potassium efflux. Phase 4 is returning back to resting membrane potential due to potassium efflux at the same time as fast sodium channels and L type calcium channels are closed.

   Bowditch effect: Also called as Treppe or Staircase effect is based on the phenomenon of increase in the force of contraction with an increase in the heart rate. It results due to an increase in the intracellular calcium. At higher heart rates, the NA/K ATPase is unable to keep up with the rate of sodium influx with each action potential. This indirectly inhibits the activity of the Na/Ca exchanger leading to an increase in intracellular calcium levels. Extra intracellular calcium also means that more calcium is sequestered by the sarcoplasmic reticulum, hence more calcium is released into the cytosol with each successive excitation-contraction coupling. The result is an increase in inotropy or force of contraction. On the other hand, a failing heart does not exhibit the Bowditch phenomenon. It shows a reverse Bowditch or negative staircase effect. Failing hearts cannot keep up with the increasing circulatory and ATP requirements and rising heart rates. This negatively affects actin-myosin cross-bridge formation. SERCA malfunction is also associated with failing hearts, and it will result in reduced intracellular calcium levels.

Post-extrasystolic potentiation (PESP): An extrasystole causes more calcium to be released into the cardiac cell that increases the force of the next contraction. An enhanced PESP measured as post-extra systolic blood pressure potentiation is an independent predictor of mortality in survivors of AMI and chronic heart failure patients.

2. Action potential of the SA node: The SA node is the pacemaker of the heart. It has the shortest refractory period, has an unstable resting membrane potential, and has 3 phases in its action potential. There is no plateau/phase 2 and phase 1. The SA node also exhibits automaticity, i.e., it can spontaneously generate action potentials. Phase 0 depolarization is slower as it is not caused by the fast sodium channels but by calcium influx through L-type calcium channels. It is followed by the phase of repolarization or phase 3, resulting from the opening of potassium channels causing potassium efflux. Next comes phase 4, or pacemaker potential or phase of spontaneous depolarization, which is a slow upstroke caused by the opening of slow sodium channels causing an influx of sodium called the “funny current”. The rate of phase 4 directly correlates with the heart rate. Interestingly, AV node action potentials resemble the SA node, but the SA node determines the heart rate as it has the fastest rate of phase 4 depolarization. Other conducting tissues of the heart take over when the SA node is not functioning, e.g., in sick sinus syndrome, ischemia, etc.

   Conduction in cardiac tissues: Action potentials generated by the SA node are first conducted across the atria. The AV node transmits the impulses from the atria to the ventricles. Conduction slows at the AV node allowing ventricular filling. From the AV node, the impulse is transmitted by the Bundle of His, then the right and left bundle branches before entering the Purkinje fibres, which distribute the impulse all over the ventricles. Purkinje fibres are the fastest conducting tissue, while the AV node is the slowest.

The velocity of cardiac conduction depends on phase 0 of the action potential or the rate of tissue depolarization. Faster conduction will increase, while slower conduction will decrease the slope of phase 0 depolarization. Sodium channel blockers decrease the conduction velocity by blocking fast sodium channels that cause phase 0 depolarization.

Chronotropy is an indicator of heart rate while dromotropy indicates conduction velocity. Sympathetic activation has a positive chronotropic and positive dromotropic effect as it increases both heart rate and conduction velocity. Parasympathetic activation has negative chronotropic and negative dromotropic effects.

Effects of autonomic system on the heart

ECG: Also called as EKG or electrocardiogram. An ECG measures the electrical activity of the heart. The following waves and segments are seen in a normal ECG:

1. P wave: It represents atrial depolarization.

2. PR interval: It starts at the onset of the P wave and ends at the beginning of the QRS complex. Normally it should be less than 0.20 seconds or 200 milliseconds. This represents the time between beginning of atrial depolarization and the beginning of ventricular depolarization. The isoelectric segment between the end of the P wave and beginning of the QRS complex called PR segment represents the time taken for conduction at the AV node.

3. QRS complex: It represents the time taken for ventricular depolarization.

4. ST segment: It is an isoelectric segment that lies between the end of QRS wave and beginning of the T wave. It corresponds to the plateau phase of the action potential.

5. T wave: It represents ventricular repolarization.

6. QT interval: It corresponds to ventricular depolarization and repolarization. It includes the QRS, ST segment and the T wave. QT interval is shorter in faster heart rates and longer in slower heart rates.