Page 121 - YORAM RUDY BOOK FINAL

P. 121

(Shimizu et al.,1997 255 and 1998 )
254

Figure 4.6. Ion channel mutations and the long QT (LQT) syndrome. Left: Reduction of I (LQT1)
Ks
reproduces the clinically observed prolongation of the QT interval without broadening of the
T-wave. Middle: Reduction of I (LQT2) prolongs the QT interval. Action potential prolongation
Kr
occurs preferentially in M cells, which have less total repolarizing current due to smaller I . The
Ks
greater differences between M-cell repolarization and repolarization of the other cell types broad-
ens the T-wave and augments its amplitude. Right: LQT3, caused by enhanced late I current
Na
(magnitude varied from 0.05% to 0.2% of peak I ) results in a delay of T-wave onset, prolongation
Na
of the QT interval, and broadening of the T-wave. The simulation results are consistent with exper-
iments, 254,255 where the three LQT syndromes were modeled pharmacologically. Reproduced from
Gima and Rudy [247]. The bottom panel is excerpted from Shimizu and Antzelevitch [254] and
[255]. All panels are reproduced with permission from Wolters Kluwers Health, Inc.

because it occurs on the background of a smaller total repolarizing current (due to reduced I
Ks
expression in these cells). Consequently, QT interval prolongation occurs with widening of the

T-wave and augmentation of its amplitude.

The Brugada syndrome manifests on the body surface ECG as ST segment elevation in the

right precordial leads (these leads are proximal to the right ventricle). The T1620M mutation in the