%0 Journal Article
%T Modelling Human Channelopathies Using Induced Pluripotent Stem Cells: A Comprehensive Review
%A Martin M¨¹ller
%A Thomas Seufferlein
%A Anett Illing
%A J£¿rg Homann
%J Stem Cells International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/496501
%X The generation of induced pluripotent stem cells (iPS cells) has pioneered the field of regenerative medicine and developmental biology. They can be generated by overexpression of a defined set of transcription factors in somatic cells derived from easily accessible tissues such as skin or plucked hair or even human urine. In case of applying this tool to patients who are classified into a disease group, it enables the generation of a disease- and patient-specific research platform. iPS cells have proven a significant tool to elucidate pathophysiological mechanisms in various diseases such as diabetes, blood disorders, defined neurological disorders, and genetic liver disease. One of the first successfully modelled human diseases was long QT syndrome, an inherited cardiac channelopathy which causes potentially fatal cardiac arrhythmia. This review summarizes the efforts of reprogramming various types of long QT syndrome and discusses the potential underlying mechanisms and their application. 1. Introduction ¡°Inherited long QT syndrome¡± comprises a group of channelopathies that cause a delayed repolarization of the heart leading to an increased risk of malignant ventricular tachycardias, in particular torsade de pointes, that imply the risk of a fatal cardiac arrest. Several attempts have been made to estimate the prevalence of long QT syndromes in the past, while older studies quantify the prevalence between 1:20000 and 1:5000. The latest analysis by Schwartz et al. provides evidence for a higher prevalence close to 1:2000 in a Caucasian population [1]. It is assumed that up to 30% of sudden unexpected deaths in infants are caused by different forms of long QT syndromes (LQTS). These data also implicate that most cases of the LQTSs are diagnosed when they become clinically apparent in an individual or his/her family. Subclinical forms of LQT syndrome can become apparent under the influence of various drugs with QT elongation capability [2]. Ion channels represent a large group of pore proteins regulating ion efflux from the inner cell to the extracellular compartment or vice versa, thereby inducing changes in the membrane potential. Activity is mainly regulated either by voltage or by certain ligands. Thereby, a variety of ion currents are regulated in various tissues. Sodium, potassium, and calcium channels are the primary representatives of ion channel families in the human heart. A complex interplay of certain ion fluxes in a defined sequence operates the cardiac action potential. Thus, it is not surprising that slight mutations can disturb the ion
%U http://www.hindawi.com/journals/sci/2013/496501/