PubMed 25254341

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv11.1 , Kv7.1 , Nav1 , Nav1.5

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

Authors: C Ian Spencer, Shiro Baba, Kenta Nakamura, Ethan A Hua, Marie A F Sears, Chi-cheng Fu, Jianhua Zhang, Sadguna Balijepalli, Kiichiro Tomoda, Yohei Hayashi, Paweena Lizarraga, Julianne Wojciak, Melvin M Scheinman, Katriina Aalto-Setälä, Jonathan C Makielski, Craig T January, Kevin E Healy, Timothy J Kamp, Shinya Yamanaka, Bruce R Conklin

Journal, date & volume: Stem Cell Reports, 2014 Aug 12 , 3, 269-81

PubMed link:

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.