Referenced in: none

Automatically associated channels: Kv7.1

Title: Disease characterization using LQTS-specific induced pluripotent stem cells.

Authors: Toru Egashira, Shinsuke Yuasa, Tomoyuki Suzuki, Yoshiyasu Aizawa, Hiroyuki Yamakawa, Tomohiro Matsuhashi, Yohei Ohno, Shugo Tohyama, Shinichiro Okata, Tomohisa Seki, Yusuke Kuroda, Kojiro Yae, Hisayuki Hashimoto, Tomofumi Tanaka, Fumiyuki Hattori, Toshiaki Sato, Shunichiro Miyoshi, Seiji Takatsuki, Mitsushige Murata, Junko Kurokawa, Tetsushi Furukawa, Naomasa Makita, Takeshi Aiba, Wataru Shimizu, Minoru Horie, Kaichiro Kamiya, Itsuo Kodama, Satoshi Ogawa, Keiichi Fukuda

Journal, date & volume: , 2012 Jul 24 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22739119

Abstract
Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs).We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells.This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine.