Cardiac K+ channels and drug-acquired long QT syndrome

The hallmark of long QT syndromes (LQTS) is an abnormal ventricular repolar ization characterized try a prolonged QT interval on the electrocardiogram and a propensity to the occurrence of syncopes resulting from polymorphic v entricular tachycardia, called torsades de pointes. They may degenerate to ventricular fibrillation, possibly causing sudden death. Congenital LQTS, w hich implicates at least six chromosomal loci, LQT1 to LQT6, three of them corresponding to mutations concerning the coding of K+ channel proteins, gi ve useful information about the mechanism underlying the arrhythmia. One of the potassium channel genes implicated in congenital LQTS is HERG, which e ncodes the I-Kr current channel protein. This current has provided a releva nt insight into the occurrence of drug-acquired LQTS, since all drugs assoc iated with torsades, such as erythromycin, terfenadine, haloperidol, or cis apride, also block I-Kr.