The year in clinical cardiac electrophysiology.

number of studies of genetic and molecular effects on rrhythmogenesis are noteworthy. ong QT syndrome (LQTS). Despite the great advances n our understanding of the role of channel disorders as auses for the LQTS, at present in at least 25% of these atients no genetic defect has been established. The idenified mutant genes are responsible for coding either the lpha (membrane spanning) or rarely the beta subunits of on channels. A very rare cause of the LQTS, for example, s caused by an abnormality in ANK2, which encodes nkyrin-B, a protein thought to be involved in the traffickng of Na and Ca channels to the cell membrane. It is he first example of a nonchannel protein disorder that ffects channel function. The proteins that make up the ion hannel are formed within the endoplasmic reticulum and oved (or trafficked) to the appropriate location in the yocardial cell membrane. Hence a channel disorder might e manifest not because of any intrinsic defect in the akeup of a specific ion channel, but because of an inability o transport the protein to the appropriate site on the embrane. aveolin-3 mutations and LQTS. More recently, attenion has been focused on the caveolae, which are microdoains found in the sarcolemma and serve both as scaffolding or ion channels as well as in signal transduction (beta-2 drenergic pathway). In a recent very important study, Vatta et al. (1) analyzed lood from 905 unrelated patients who underwent genetic esting for LQTS. They also showed that caveolin-3 coloalizes with the voltage-gated Na channel (h Nav 1.5) in uman myocardium and identified 4 novel mutations in AV-3, which encodes caveolin-3 protein.