Individuals with congenital or acquired prolongation of the QT interval, or long 
QT syndrome (LQTS), are at risk of life-threatening ventricular arrhythmia. LQTS 
is commonly genetic in origin but can also be caused or exacerbated by 
environmental factors. A missense mutation in the L-type calcium channel 
Ca(V)1.2 leads to LQTS in patients with Timothy syndrome. To explore the effect 
of the Timothy syndrome mutation on the electrical activity and contraction of 
human cardiomyocytes, we reprogrammed human skin cells from Timothy syndrome 
patients to generate induced pluripotent stem cells, and differentiated these 
cells into cardiomyocytes. Electrophysiological recording and calcium (Ca(2+)) 
imaging studies of these cells revealed irregular contraction, excess Ca(2+) 
influx, prolonged action potentials, irregular electrical activity and abnormal 
calcium transients in ventricular-like cells. We found that roscovitine, a 
compound that increases the voltage-dependent inactivation of Ca(V)1.2 (refs 
6-8), restored the electrical and Ca(2+) signalling properties of cardiomyocytes 
from Timothy syndrome patients. This study provides new opportunities for 
studying the molecular and cellular mechanisms of cardiac arrhythmias in humans, 
and provides a robust assay for developing new drugs to treat these diseases.