Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome
J. Clin. Invest. Michael Brunner, et al. 118:2246 doi:10.1172/JCI33578 [
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Figure 6Cellular electrophysiology. (
A) APD of rabbit ventricular myocytes. Left panel shows typical action potential recordings (0.1 Hz) from LMC, LQT1, and LQT2 rabbits. Right shows averaged APD (APD
90, mean ± SEM) of LMC (354.05 ± 30.07 ms,
n = 22), LQT1 (499.88 ± 45.71 ms,
n = 14), and LQT2 rabbits (533.14 ± 54.22 ms,
n = 14); *
P < 0.05. (
B) Isolation and quantification of
IKr and
IKs. Left panel shows original recordings of control, LQT1, and LQT2 rabbits as indicated. After a recording without drugs (a), the cells were perfused with 5 μM E-4031 (b) and
IKr was defined as the E4031-sensitive current (d). Secondary to E4031 application, the cells were further perfused with 30 μM chromanol 293B (c) and
IKs was defined as chromanol-sensitive current (e). Right panels shows quantification of
IKr and
IKs. Current amplitudes measured at the end of repolarization (
IKs or
IKr) and the peak of the tail (
IKs tail or
IKr tail) were plotted against membrane voltages. All currents were normalized to cell capacitance. Open circles depict control myocytes (
n = 20 from 6 rabbits), filled circles depict LQT1 myocytes (
n = 17 from 5 rabbits), and filled triangles depict LQT2 myocytes (
n = 12 from 3 rabbits). The downregulation of
IKr (in LQT1) or
IKs (in LQT2) was significant compared with controls (
P < 0.05 by 2-way ANOVA). (
C)
Ito current and
IK1 currents. Standard current-voltage relationship (IV curve) of Ito (left panel) or quasi-IV curve of IK1 (right panel) revealed no significant differences in peak Ito currents (n = 6–8) or IK1 currents (right, n = 10–12) among LMC, LQT1, and LQT2 rabbits.
