Reply to Christ et al.: LQT1 and JLNS phenotypes in hiPSC-derived cardiomyocytes are due to KCNQ1 mutations

Concerning the role of IKs under baseline conditions, we would like to point out that this is more controversial than Christ et al suggest

Boris Greber

2015

Scholarcy highlights

  • Concerning the role of IKs under baseline conditions, we would like to point out that this is more controversial than Christ et al suggest
  • In their letter on our recent publication on modeling Jervell and Lange-Nielsen syndrome using human induced pluripotent stem cell-derived cardiomyocytes, Christ et al question: the role of the delayed rectifier potassium current under baseline conditions in the absence of sympathetic stimulation, the rapid activation kinetics of IKs, and the causality of mutant KCNQ1 in the disease phenotypes we observed in hiPSCCMs
  • The conclusion that IKs plays no role in repolarization under resting conditions has been challenged using an IKs inhibitor, JNJ303, with improved potency
  • Given the known immaturity of hiPSC-CMs, it is conceivable that this phenotype was more pronounced than in primary cardiomyocytes in vivo
  • Concerning the question of whether KCNQ1 mutations cause the observed phenotypes, we wish to point out that in both of our JLNS models, we used genetic engineering to create isogenic pairs of hiPSC lines that only differed in the mutation
  • Challenge the validity of hiPSC-CMs as models of human cardiac health and disease in general , and we certainly agree that further investigation is necessary to establish conditions under which hiPSC-CMs have added value

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