Cardiac Action Potential - Rhythmicity

Overview

Given the importance of rhythmic contraction of the heart to survival, it is not surprising that the organ possess internal, autonomous mechanisms for initiating and propagating Cardiac Action Potentials of regular periodicity. Rhythmic Cardiac Action Potentials are initiated by specialized "Pacemaker" cardiomyocytes which can uniquely self-excite with regular periodicity. We first discuss the shape and molecular mechanism of this rhythmic self-excitation and then discuss the locations of such specialized cells within the heart.

Shape

The electrophysiological shape of self-exiting, rhythmic cardiac action potentials is qualitatively different than Cardiac Action Potentials observed in other cardiomyocytes which do not display self-excitatory properties (These are described in Cardiac Action Potential - Cellular Basis). An important difference is the fact that in self-exciting cells, the resting membrane potential is maximally -55mV to -60mV rather than the -90mV of other cardiomyocytes. Three phases of the membrane potential can be distinguished in self-exciting cells termed the Slow Depolarization, Rapid Depolarization, and Repolarization Phases. Although the terms "Rapid" are used above, it should be noted that the rate of change of the membrane potential in these phases is still significantly slower than membrane potential changes of normal cardiomyocytes described in Cardiac Action Potential - Cellular Basis.

Slow Depolarization: Characterized by a gradual, creeping depolarization from the resting membrane to roughly -40mV. Rapid Depolarization: Characterized by a relatively rapid depolarization to a lightly positive membrane potential of 0mV to +10mV. Repolarization: Characterized by a relatively rapid repolarization to the resting membrane potential of -55mV to -60mV.

Molecular Mechanism

Three basic ion channels are responsible for the unique, self-exciting Cardiac Action Potential described above.

Funny Sodium Channels display low-level conductance to positively-charged Na⁺ ions and open in response to states of membrane hyperpolarization. Consequently, when the resting membrane potential is reached, Funny sodium channels open and allow low-grade, inward current of positive charge, termed I_funny which is responsible for the Slow Depolarization phase.

Transient, T-type Calcium Channels are voltage-gated and open when the critical threshold membrane potential of roughly -40mV is reached. These channels allow rapid entry of substantial amounts of positively charged Ca⁺⁺ ions and are responsible for the Rapid Depolarization phase. However, opening of these channels is transient and they begin to close about a hundred milliseconds after their opening.

The Slow Potassium Channels open with a delay following the Rapid Depolarization phase and allow rapid efflux of positively charged K⁺ ions from the cell. This delayed yet large outward current of positive charge is responsible for the Rapid Repolarization phase. However, these potassium channels then close once resting potential is reached which in turn activates the Funny Sodium Channels. In this way, return to resting potential immediately initiates the next round of Slow Depolarization.

Pacemaker Locations

Although we have described rhythmic, self-excitation as a unique property of specialized cardiomyocytes, the reality is that all cardiomyocytes can theoretically display self-excitatory behavior. In fact, any cardiomyocyte placed in isolation within a cell culture dish will begin to rhythmically self-excite. However, it is clearly important that only one locus of cells within the organ display rhythmic, self-excitation as more than one "Pacemaker" could easily derange coordinated pumping of the heart and thus lead to serious arrhythmias. The phenomenon which ensures that the existence of only one pacemaker in the entire organ is known as "Overdrive Suppression", described below.

Overdrive Suppression describes the phenomenon that the fastest pacemakers in the heart inhibit rhythmic, self-excitation by other cardiomyocytes. Therefore, if a cardiomyocyte is receiving regular depolarizing currents from adjacent cardiomyocytes at a faster frequency than its own I_funny can cause, then it will simply display the traditional cardiac action potential described in Cardiac Action Potential - Cellular Basis. Consequently, the locus of cardiomyocytes which self-excite with the fastest frequency ultimately control the rhythmic beating of the entire organ. The molecular mechanism of Overdrive Suppression is not well-understood and is beyond the scope of this text. Different loci within cardiac tissue display a wide range of self-excitatory frequency and based on there relative self-excitatory rates, the sole pacemaker of the organ can be predicted.

SA Node: Cardiomyocytes within the SA Node always display the fastest self-excitatory periodicity in the normal heart and thus emerge as the sole Pacemaker in healthy individuals.
AV Node: Cardiomyocytes within the [AV Node display the next fastest self-excitatory periodicity and usually emerge as the primary pacemaker in the event of SA Node damage.
Purkinje Fibers: Cardimyocytes within the bundle of His display the next fastest self-excitatory periodicity followed by the remainder of the Purkinje Fibers throughout the ventricle. Consequently, these loci emerge as the Pacemakers given SA and AV node damage.
Because the SA Node is considered the pacemaker in the normal heart, the other potential pacemaker loci are termed "Ectopic Pacemakers" when they take on the responsibility of pacing the heart. Note that the order of pacemakers roughly follows the order of tissues which are activated during propagation of the cardiac action potential.

GoozyGooz