Fundamentals of Cardiac Electrophysiology

Fundamentals of Cardiac Electrophysiology encompass the essential principles and mechanisms underlying the generation, propagation, and regulation of electrical activity in the heart. This field integrates cellular, tissue, and organ-level processes that coordinate the rhythmic contraction of the myocardium, ensuring effective blood circulation. It involves studying the electrical excitability of cardiac cells, the sequence of electrical activation and recovery, and the spatial-temporal organization of electrical signals that govern heartbeat coordination.

Cardiac Electrical Excitability

Cellular Basis of Excitability

Cardiac excitability begins at the cellular level with the cardiac myocytes, which possess the ability to generate and propagate action potentials. This property arises from the controlled movement of ions across the cell membrane via specialized ion channels. The resting membrane potential of cardiac cells is typically around -85 to -95 millivolts, maintained primarily by potassium ion gradients. Excitability is initiated when a stimulus causes depolarization, leading to the opening of voltage-gated sodium channels and the rapid influx of sodium ions, triggering the action potential's upstroke.

Ion Channels and Currents

Several ion channels contribute to the cardiac action potential phases:

• Fast sodium channels (Na⁺): Responsible for rapid depolarization (Phase 0).
• Transient outward potassium channels (K⁺): Contribute to early repolarization (Phase 1).
• L-type calcium channels (Ca²⁺): Sustain the plateau phase (Phase 2), vital for excitation-contraction coupling.
• Delayed rectifier potassium channels (K⁺): Mediate repolarization (Phase 3).
• Inward rectifier potassium channels (K⁺): Maintain resting potential (Phase 4).

The interplay of these currents shapes the characteristic cardiac action potential, which differs among various cardiac tissues such as atrial myocytes, ventricular myocytes, and specialized conduction system cells.

Excitability Threshold and Refractoriness

Cardiac cells have a threshold potential that must be surpassed for an action potential to occur. After excitation, cells enter a refractory period during which re-excitation is impossible (absolute refractory period) or requires a stronger stimulus (relative refractory period). These periods ensure unidirectional conduction and prevent premature re-excitation, crucial for maintaining rhythmic heartbeat.

Electrical Excitation and Recovery

Action Potential Phases

The cardiac action potential unfolds in a sequence of phases:

• Phase 0 (Depolarization): Rapid Na⁺ influx through voltage-gated channels.
• Phase 1 (Initial Repolarization): Transient K⁺ outward current.
• Phase 2 (Plateau): Balance of inward Ca²⁺ currents and outward K⁺ currents, prolonging depolarization.
• Phase 3 (Repolarization): Dominant K⁺ efflux restoring resting potential.
• Phase 4 (Resting phase): Stable resting membrane potential maintained by ion pumps and leak channels.

This sequence allows the heart muscle to contract and relax in a coordinated manner.

Excitation-Contraction Coupling

The influx of calcium during the plateau phase triggers calcium-induced calcium release from the sarcoplasmic reticulum, leading to muscle contraction. The subsequent repolarization reduces intracellular calcium, allowing relaxation.

Recovery and Refractoriness

Recovery involves the restoration of ion gradients and membrane potential, preparing cells for the next excitation. The refractory periods prevent premature or abnormal beats and contribute to the timing of cardiac cycles.

Cardiac Electrical Activation

Pacemaker Activity

Specialized pacemaker cells in the sinoatrial (SA) node generate spontaneous depolarizations due to a slow diastolic depolarization driven by "funny" (If) currents, T-type calcium currents, and decreasing potassium conductance. This automaticity sets the heart rate.

Conduction System

Electrical impulses propagate from the SA node to the atrioventricular (AV) node, bundle of His, bundle branches, and Purkinje fibers. The conduction system ensures rapid and coordinated activation of atrial and ventricular myocardium.

Activation Sequence

• Atrial activation: Rapid depolarization initiates atrial contraction.
• AV node delay: Allows ventricles to fill before contraction.
• Ventricular activation: Coordinated spread through Purkinje fibers leads to synchronous ventricular contraction.

Alterations in this sequence can lead to arrhythmias or conduction blocks.

Electrical Coordination of the Heartbeat

Synchronization of Cardiac Cells

Cardiac myocytes are electrically coupled via gap junctions composed of connexin proteins, permitting the passage of ions and small molecules. This coupling ensures that action potentials propagate smoothly and synchronously across myocardial tissue.

Conduction Velocity and Anisotropy

Conduction velocity varies across cardiac regions due to differences in cell size, gap junction density, and fiber orientation. The anisotropic nature of cardiac tissue means electrical impulses travel faster along the longitudinal axis of fibers than across the transverse axis, optimizing contraction efficiency.

Electrocardiogram (ECG) Correlates

The coordinated electrical activity generates measurable potentials on the body surface, recorded as the ECG. The P wave represents atrial depolarization, the QRS complex ventricular depolarization, and the T wave ventricular repolarization. Understanding these components is essential for diagnosing cardiac electrical abnormalities.

Spatial and Temporal Scales of Cardiac Electrophysiology

Cellular Level

At the microscale, individual ion channel function, intracellular calcium dynamics, and action potential morphology define excitability and conduction.

Tissue Level

At the mesoscale, cell-to-cell coupling, tissue architecture, and heterogeneity influence impulse propagation, refractoriness, and susceptibility to arrhythmias.

Organ Level

At the macroscale, the integrated conduction system and myocardial electrical activity coordinate heartbeats. Spatial heterogeneity in repolarization and conduction velocity can predispose to complex arrhythmogenic substrates.

Temporal Dynamics

Cardiac electrical events occur over milliseconds to seconds, with rapid depolarization phases and longer refractory and recovery periods governing heart rhythm and rate adaptability.

Electrophysiological State and Electrical Variables

Membrane Potential

The membrane potential (Vm) reflects the voltage difference across the cell membrane, a key determinant of excitability and conduction.

Ionic Currents

The net flow of ions defines the membrane potential changes and action potential phases. These currents are dynamic and modulated by autonomic inputs, pharmacological agents, and pathological conditions.

Refractory Periods

Absolute and relative refractory periods define the electrophysiological state, influencing the timing and propagation of successive impulses.

Excitability and Conduction Velocity

Excitability depends on the availability of sodium channels and resting membrane potential, while conduction velocity is affected by cell coupling, fiber orientation, and membrane properties.

Electrochemical Gradients and Nernst Potential

The driving force for ion movement is determined by electrochemical gradients, described by the Nernst equation, which calculates the equilibrium potential for each ion species.

Where E is the equilibrium potential, R the gas constant, T absolute temperature, z the ion valence, and F Faraday's constant.

This comprehensive framework of the fundamentals of cardiac electrophysiology provides the basis for understanding normal cardiac function as well as the pathophysiology of arrhythmias, conduction disturbances, and the therapeutic mechanisms of antiarrhythmic drugs and devices.