ReviewCardiac channelopathies: Genetic and molecular mechanisms

Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012.

► Mutations in the genes coding for cardiac ion channels lead to arrhythmias. ► Cardiac channelopathies may lead to sudden cardiac death. ► Cardiac channelopathies are characterized by genetic and mechanistic heterogeneity. ► Congenital long QT syndrome and Brugada syndrome are the most frequent phenotypes. ► Understanding the molecular mechanisms of channelopathies may lead to new treatments.