Cellular basis for the repolarization waves of the ECG

Abstract

One hundred years after Willem Einthoven first recorded the electrocardiogram (ECG), physicians and scientists are still debating the cellular basis for the various waves of the ECG. In this review, our focus is on the cellular basis for the J, T, and U waves of the ECG. The J wave and T wave are thought to arise as a consequence of voltage gradients that develop as a result of the electrical heterogeneities that exist within the ventricular myocardium. The presence of a prominent action potential notch in epicardium but not endocardium gives rise to a voltage gradient during ventricular activation that inscribes the J wave. Transmural and apico-basal voltage gradients developing as a result of difference in the time course of repolarization of the epicardial, M, and endocardial cell action potentials, and the more positive plateau potential of the M cell contribute to inscription of the T wave. Amplification of these heterogeneities results in abnormalities of the J wave and T wave, leading to the development of the Brugada, long QT, and short QT syndromes. The basis for the U wave has long been a matter of debate. One theory attributes the U wave to mechanoelectrical feedback. A second theory ascribes it to voltage gradients within ventricular myocardium and a third to voltage gradients between the ventricular myocardium and the His-Purkinje system. Although direct evidence in support of any of these three hypotheses is lacking, recent studies involving the short QT syndrome have generated renewed interest in the mechanoelectrical hypothesis.

FIGURE 1

Hypothermia-induced J wave. Each panel shows transmembrane action potentials from the epicardial (Epi) and endocardial (Endo) regions of an arterially perfused canine left ventricular wedge and a transmural ECG simultaneously recorded. (A): A small but distinct action potential notch in epicardium but not in endocardium is associated with an elevated J point at the R-ST junction (arrow) at 36°C. (B): A decrease in the temperature of the perfusate to 29°C results in an increase in the amplitude and width of the action potential notch in epicardium but not endocardium, leading to the development of a transmural voltage gradient that manifests as a prominent J wave on the ECG (arrow). (Modified from Ref. with permission.)

FIGURE 2

Voltage gradients on either side of the M region and the inscription of the T wave. Top: Action potentials simultaneously recorded from endocardial, epicardial, and M region sites of an arterially perfused canine left ventricular wedge preparation. Middle: ECG recorded across the wedge. Bottom: Computed voltage differences between the M-Epi action potentials (ΔV_M–Epi) and between the M region and endocardium responses (ΔV_Endo–M). If these traces are representative of the opposing voltage gradients on either side of the M region, responsible for inscription of the T wave, then the weighted sum of the two traces should yield a trace (middle trace in bottom grouping) resembling the ECG, which it does. (A): Control. (B): Hypokalemic conditions ([K⁺]_o = 1.5 mM) + dl-sotalol (100 uM). Basic cycle length (BCL) = 1,000 msec. (Modified from Ref. with permission.)

FIGURE 3

Correlation of transmembrane and electrocardiographic activity. Action potentials from epicardium (Epi), midmyocardium (M), and subendocardial Purkinje were recorded simultaneously with a transmural ECG from a canine arterially perfused left ventricular wedge preparation. Note that although repolarization of the subendocardial Purkinje fiber occurs after that of the M cell, it does not register on the ECG. BCL = 2,000 msec. (Modified from Ref. with permission.)

FIGURE 4

Precordial ECG leads recorded from a patient with the short QT syndrome showing a prominent separation of the T and U waves. (Modified from Ref. with permission.)