Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia

Stem Cell Reports
C Ian SpencerBruce R Conklin


Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca(2+)]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca(2+)]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca(2+). Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca(2+)]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na(+)-Ca(2+) exchange. These results suggest that LQTS mutations act partly on cytosolic Ca(2+) cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.


Dec 1, 1991·European Heart Journal·C T JanuaryJ C Makielski
Mar 1, 1991·Journal of Neuroscience Methods·J RaeM Watsky
Jul 1, 1984·American Heart Journal·L T Iseri, J H French
Feb 14, 1998·The Journal of Biological Chemistry·A E DoeringK D Philipson
Nov 24, 1999·Lancet·S Viskin
Mar 15, 2000·Journal of the American College of Cardiology·W Shimizu, C Antzelevitch
Jan 24, 2002·Nature·Eduardo Marbán
May 9, 2003·The New England Journal of Medicine·G Michael Vincent
Aug 23, 2003·American Journal of Physiology. Heart and Circulatory Physiology·C Ian Spencer, James S K Sham
Nov 18, 2003·The Journal of Physiology·Min WangJoshua R Berlin
Aug 3, 2005·The Journal of Clinical Investigation·Arthur J Moss, Robert S Kass
Aug 3, 2005·The Journal of Clinical Investigation·Dan M Roden, Prakash C Viswanathan
May 12, 2006·Journal of Cardiovascular Electrophysiology·Eric A SobieW J Lederer
Jan 11, 2007·Journal of Cardiovascular Electrophysiology·Donglin GuoGan-Xin Yan
Nov 7, 2008·Journal of Pharmacological Sciences·Kaichiro KamiyaMichael C Sanguinetti
Jul 14, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Lin WuLuiz Belardinelli
Dec 2, 2009·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Jamal Nasir KhanJames Michael Glancy
Apr 8, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiaoya XiFrank Pillekamp
Jul 3, 2010·Molecular Genetics and Metabolism·Nilesh J BokilKim M Summers
Oct 6, 2010·Journal of Molecular and Cellular Cardiology·Ihor ZahanichVictor A Maltsev
Jan 18, 2011·Nature·Ilanit ItzhakiLior Gepstein
Mar 25, 2011·Clinical Pharmacology and Therapeutics·H Inoue, S Yamanaka
Oct 26, 2011·The Journal of Physiology·Roshni V MadhvaniRiccardo Olcese
Nov 5, 2011·Disease Models & Mechanisms·Anna L LahtiKatriina Aalto-Setälä
Jun 28, 2012·Biophysical Journal·Marvin G ChangM Roselle Abraham
Jan 2, 2013·The Journal of General Physiology·Cecile TerrenoireRobert S Kass

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Methods Mentioned

fluorescence microscopy
genetic modification

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