Cardiac electrophysiology

Introduction

The heart contains specialized tissue for: (1) generating rhythmic action potentials and (2) conducting those action potentials precisely across the heart. This ensures correct timing of atrial and ventricular contraction.

System structure

Fig. 11.1 depicts the typical pathway of cardiac excitation.

Action potentials are transmitted from sinoatrial (SA) node to atrioventricular (AV) node.
Excitation proceeds through atrial muscle and specialized conducting tissues:
- His bundle
- Bundle branches
- Purkinje fibers
Impulses reach ventricular muscle, initiating muscle contraction.

Fig. 11.1, Pacemaker and conductive tissues of the myocardium. Left, Anatomic locations of the various conductive tissues. Right, Action potentials in the various tissues. AV , Atrioventricular; SA , sinoatrial.

Coordinated muscular contraction requires the rapid transmission of electrical impulses, which is facilitated by the gap junctions between myocardial cells.

Gap junctions make the myocardium a functional syncytium (many cells that make the heart function as though it were a single continuous unit of cytoplasm).
As a result, a stimulus arising at any one point within the ventricle leads to the contraction of both left and right ventricles; likewise, a stimulus arising within the atria leads to the contraction of both left and right atria.

The SA node is normally the functional pacemaker of the heart.

Under certain pathologic conditions, cells outside the sinus node (within the atria, the AV junction, or the ventricles) may act as independent pacemakers and generate their own intrinsic rhythm for the heart.
Automaticity is the ability to generate impulses spontaneously, whether innate or acquired as in pathologic states (see Clinical Correlation Box 11.1 ).

Clinical Correlation Box 11.1

Ectopic automaticity (misplaced automaticity) is important to understanding some of the common cardiac arrhythmias (rhythm disturbances) and electrocardiographic abnormalities seen in clinical practice.

Conduction, the capacity to generate action potentials cell to cell at regular intervals, is another property of myocardial tissue that varies throughout the transmission pathway.

Speed of conduction varies depending on the location.
- (Fastest) Purkinje fibers → Atrial muscle → Ventricular muscle → AV node (slowest).
- Slow conduction at the AV node ensures that the ventricles have adequate time to fill before the signal for ventricular contraction arrives.
- Differences in conduction vary depending on type of action potentials arising there.

System function

Cardiac electrophysiology

Action potentials provide electrical stimulation that is coupled to rhythmic contraction of the heart. Two principal types observed in the heart ( Fig. 11.2 ).

Fast response seen in conductive cardiac tissue (the myocardial fibers in the atrium, ventricles, His bundle, and Purkinje fiber network).
Slow response, distinguished by a more prolonged upstroke in electrical potential, seen in the pacemaker fibers of the SA and AV nodes.
- Only the slow fibers possess automaticity.
- The slow response is distinguished by smaller amplitude, as well as a slower upstroke (phase 0). This accounts for lower conduction velocity relative to fast-response fibers.

Fig. 11.2, Fast and slow action potentials. Notice the automatic upturn in electrical potential in phase 4 of the slow response.

Resting potential

The sarcolemma of each myocyte is hydrophobic and thus will not permit entry of most charged, hydrophilic ions. Various phases of the cardiac action potential in both slow-response and fast-response fibers can be explained by changes in the permeability of the cell membrane to various ions, primarily:

Sodium (Na ⁺ )
Potassium (K ⁺ )
Calcium (Ca ² ⁺ )

These variations in permeability are accomplished through variations in the configuration and conductance of specialized transmembrane proteins known as ion channels.

Ion channels have two important functional properties:

Selectivity is the ability of different channels to be selective for specific ions, such as Na ⁺ or K ⁺ .
Gating is a property that makes ion channels fluctuate between “open” and “closed” states in a voltage-sensitive fashion (i.e., the channel state depends on the electrical potential across the cell membrane at any given time).
- The total ionic current that flows through the channel is determined by the proportion of time spent in the open versus the closed state.

Myocardial cells, like other cells in the body, are highly permeable to K ⁺ in their resting state. This permeability to K ⁺ creates a resting membrane potential, as described in Fig. 11.3 .

The two main driving forces of permeability are electrical forces (as represented by the transmembrane voltage) and chemical forces (as represented by the concentration gradient).
When electrical forces (accumulation of electronegativity in the intracellular space) equal chemical forces (high intracellular K ⁺ concentration), equilibrium is achieved.
The electrical potential inside the cell membrane at this point is known as the equilibrium potential.

Fig. 11.3, Generation of the potassium (K + ) equilibrium potential. The Na + ,K + -ATPase drives K + into cells, generating high intracellular concentrations and thus creating a favorable chemical gradient for K + to diffuse outside the cell. This movement to the extracellular space generates increasing electronegativity on the inside of the cell (K + is a positive ion!) and thus decreases the K + efflux. Eventually, the electrostatic (K + flows in) and chemical forces (K + flows out) are equal, producing equilibrium. The black arrows indicate the direction of movement favored by the chemical gradient. The red arrows indicate the direction of movement favored by the electrical gradient.

Recall that the Nernst equation relates the equilibrium potential for an ion to intracellular and extracellular concentrations:

E _K = RT/zF ln [K ⁺ _o ]/[K ⁺ _i ]

where [K ⁺ o] is the extracellular concentration, [K ⁺ _i ] is the intracellular concentration, and E _K is the electrical potential inside the cell. (The other terms of the equation are R, the ideal gas constant, 8.314 J/mol K; T, the absolute temperature in degrees Kelvin; z, the valence of K ⁺ ; and F, the Faraday constant, 9.648 × 10 ⁴ C/mol; ln signifies the natural log function.)

Algebraic manipulation of this equation yields:

E _K = 61.5/z log [K ⁺ _o ]/[K ⁺ _i ].

The Goldman equation is a variation of the Nernst equation that calculates the equilibrium concentration of a membrane with permeabilities to many ions (K ⁺ , Ca ²⁺ , Na ⁺ , Cl ^– ) and that factors in the degree of permeability for each ion.

Table 11.1 shows the distribution of Na ⁺ , K ⁺ , and Ca ²⁺ across cardiac cell membranes and the equilibrium potentials that would exist for each if each were the only ion permeability in the membrane.

Positive potential indicates a net influx of that ion.
Negative potential indicates a net efflux of that ion.

TABLE 11.1

Ion Distributions and Individual Equilibrium Potentials

Ion	Extracellular Concentration	Intracellular Concentration	Equilibrium Potential
Na ⁺	145 mM	10 mM	70 mV
K ⁺	4 mM	135 mM	–94 mV
Ca ²⁺	2 mM	0.0001 mM	132 mV

The true resting potential of the cardiac cell membrane, reflecting the resting permeability to these three ions, is –90 mV.

Note that this is close to the Nernst potential for K ⁺ , reflecting that the resting cell membrane is permeable primarily to K ⁺ ions and not Na ⁺ or Ca ²⁺ .
- At rest, the cell membrane has a slow inward leak of sodium ions that slightly depolarizes the membrane relative to E _k .
Hyperpolarization occurs when ion flux renders the cell interior more negative, exaggerating the resting charge difference.
Depolarization occurs when ion flux renders the cell interior more positive, abolishing the resting charge difference.

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Introduction

System structure

System function

Cardiac electrophysiology

Resting potential

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Appendix 5

Appendix 4

Appendix 3

Appendix 2