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Addendum

Human iPS cell models of Jervell and Lange-Nielsen syndrome

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Article: e1012978 | Received 23 Dec 2014, Accepted 25 Jan 2015, Published online: 17 Mar 2015

Figures & data

Figure 1. Functional expression of the KCNQ1 and HERG ion channel genes in hiPSC-CMs and rescue of JLNS hiPSC-CMs. (A) Induction kinetics of the KCNQ1 and HERG genes upon long-term culture of hiPSC-CMs. Spontaneous beating is first observed at ∼1 wk. 0 wk cells are undifferentiated hiPSCs. Data denote mean values ± SEM from independent experiments (qRT-PCR data). (B) Drug testing of ∼4 wk-old wild-type hiPSC-CMs on MEA chips using specific hERG (E4031) and KvLQT1 (C293B, chromanol 293B) inhibitors. Note that the T wave-like peak is reversibly shifted toward increased field potential (FP) durations upon addition of these molecules (representative MEA recordings). (C) Transgenic rescue of JLNS hiPSC-CMs using inducible KCNQ1 expression. Doxycycline (DOX) addition induces KCNQ1 leading to FPD shortening (representative MEA spectra).

Figure 1. Functional expression of the KCNQ1 and HERG ion channel genes in hiPSC-CMs and rescue of JLNS hiPSC-CMs. (A) Induction kinetics of the KCNQ1 and HERG genes upon long-term culture of hiPSC-CMs. Spontaneous beating is first observed at ∼1 wk. 0 wk cells are undifferentiated hiPSCs. Data denote mean values ± SEM from independent experiments (qRT-PCR data). (B) Drug testing of ∼4 wk-old wild-type hiPSC-CMs on MEA chips using specific hERG (E4031) and KvLQT1 (C293B, chromanol 293B) inhibitors. Note that the T wave-like peak is reversibly shifted toward increased field potential (FP) durations upon addition of these molecules (representative MEA recordings). (C) Transgenic rescue of JLNS hiPSC-CMs using inducible KCNQ1 expression. Doxycycline (DOX) addition induces KCNQ1 leading to FPD shortening (representative MEA spectra).

Figure 2. Stress-induced arrhythmia in JLNS hiPSC-CMs (representative MEA recordings). Left: Untreated cells beating spontaneously at a frequency of ∼0.5–1 Hz. Right: Administration of cisapride or isoprenaline induces arrhythmia in JLNS hiPSC-CMs. Note the torsade de point-like shape of the MEA spectrum under adrenergic stress conditions.

Figure 2. Stress-induced arrhythmia in JLNS hiPSC-CMs (representative MEA recordings). Left: Untreated cells beating spontaneously at a frequency of ∼0.5–1 Hz. Right: Administration of cisapride or isoprenaline induces arrhythmia in JLNS hiPSC-CMs. Note the torsade de point-like shape of the MEA spectrum under adrenergic stress conditions.