Pacemaker cells and the cardiac conduction system
Pacemaker cells (rhythm drivers) are located in the sinoatrial node and are part of the cardiac conduction system. This system is formed by a collection of atypical cardiomyocytes. They are called atypical because they do not participate in myocardial contraction: their function is to generate excitation and transmit it to the working myocardium.
The main feature of pacemaker cells is that excitation in them occurs spontaneously (automatically), without an external stimulus. The explanation for this phenomenon lies at the level of the molecular mechanisms of membrane ion channels.
Electrophysiological features of an atypical cardiomyocyte
The action potential of an atypical cardiomyocyte differs from that of a skeletal muscle cell and a working cardiomyocyte in several parameters:
- Lower amplitude: the membrane charge changes from approximately −60 mV to +20 mV, i.e., about 80 mV. For comparison, in skeletal muscle, the amplitude reaches ~120 mV (from −90 to +30 mV).
- Less negative initial charge (about −60 mV). This is due to the high intrinsic permeability of the membrane to sodium and calcium: these cations continuously enter the cell and keep the membrane charge in a more positive range.
- Absence of the plateau phase characteristic of the working cardiomyocyte.
- Absence of a true resting potential: between action potentials, the membrane charge does not remain constant but changes slowly.
Slow diastolic depolarization
Instead of a resting potential, pacemaker cells exhibit slow diastolic depolarization (SDD)—a gradual shift of the membrane charge in the positive direction during the period between action potentials.
SDD is caused by the influx of sodium ions into the cell through sodium channels. Since membrane permeability to sodium is high, ions move into the cell down their concentration gradient, bringing a positive charge. This current continues until the sodium channels enter an inactivated state.
The sodium voltage-gated channel has two sets of gates—activation and inactivation—and three states:
- Closed: activation gates are closed, inactivation gates are open.
- Open: both types of gates are open, ions pass freely through the channel.
- Inactivated: inactivation gates are closed, activation gates are open.
Upon reaching a membrane charge of about −50 mV (approximately after two-thirds of SDD), the sodium channels inactivate, and sodium influx stops.
Phases of the pacemaker action potential
After sodium channel inactivation, slow calcium channels come into play. It is the calcium influx that initiates the depolarization phase, which distinguishes the atypical cardiomyocyte from other excitable cells where depolarization is generated by sodium.
- Depolarization: slow calcium channels open, Ca²⁺ ions enter the cell bringing a positive charge; the membrane potential reaches approximately +20 mV.
- Repolarization: calcium channels inactivate, and potassium channels open. Potassium, as an intracellular cation, leaves the cell down its concentration gradient, carrying away a positive charge. The membrane charge returns to −60 mV.
After repolarization, the cycle repeats: slow diastolic depolarization begins anew, and a new action potential is formed.
Mechanism of spontaneous excitation
In most excitable cells (e.g., skeletal muscle), the generation of an action potential requires a stimulus—a trigger that alters membrane permeability to sodium. Thus, for a skeletal muscle cell, such a stimulus is an impulse arriving via a motor neuron axon: it increases sodium permeability, opens channels, and triggers depolarization.
In atypical cardiomyocytes, an external stimulus is not required. The reason is the apriori high membrane permeability to sodium. Sodium channels are initially in an open state, and sodium continuously enters the cell, providing slow diastolic depolarization. After channel inactivation and subsequent repolarization, the channels return to the open state again, and the process repeats automatically.
It is this feature of ion permeability that underlies cardiac automacity and ensures the rhythmic generation of impulses by the sinoatrial node cells without external stimulation.
Key points
- Pacemaker cells are atypical cardiomyocytes of the sinoatrial node that generate excitation for the cardiac conduction system.
- The pacemaker action potential has a smaller amplitude (≈80 mV), starts from −60 mV, and lacks a plateau phase.
- There is no true resting potential; it is replaced by slow diastolic depolarization driven by sodium influx.
- Depolarization is initiated by calcium entering through slow calcium channels, rather than sodium as in other excitable cells.
- Repolarization is ensured by potassium efflux through potassium channels.
- The sodium channel has three states: closed, open, and inactivated; inactivation occurs at a charge of about −50 mV.
- The spontaneity of excitation is explained by the initially high membrane permeability to sodium—no external stimulus is required.
- This molecular mechanism underlies the automaticity of the heart.