Key result
Exposure to low extracellular potassium prolonged field potential and action potential durations in a concentration-dependent manner, with LQT1-CMs being more sensitive than wild-type CMs.
Why the study?
Does low extracellular potassium prolong repolarization and evoke early afterdepolarizations in hiPSC-derived cardiomyocytes from patients with LQT1 compared to healthy controls?
Does low extracellular potassium prolong repolarization and evoke early afterdepolarizations in hiPSC-derived cardiomyocytes from patients with LQT1 compared to healthy controls?
hiPSC-derived cardiomyocytes from LQT1 patients are more sensitive to low extracellular potassium than healthy controls, demonstrating their utility as a platform to study acquired LQTS.
Hypokalemia may heighten repolarization risk in LQT1; leaves open clinical translation and prospective validation.
Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K+. Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K+ concentration ([K+]Ex) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1. The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K+]Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K+]Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K+]Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K+]Ex and provide a platform to study acquired LQTS.
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Kuusela et al. (2017) studied Long QT syndrome (LQTS). Low extracellular potassium concentration ([K+]Ex) vs. Normal extracellular potassium / Wild-type cardiomyocytes was evaluated on Field potential durations (FPDs) and action potential durations (APDs). Exposure to low extracellular potassium prolonged field potential and action potential durations in a concentration-dependent manner, with LQT1-CMs being more sensitive than wild-type CMs.
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