In recent years, the progress of molecular genetics of inherited arrhythmogenic diseases portrays an unexpected complexity of clinical phenotypes associated with mutations in several genes that control cardiac excitability. Among the most recent findings, the voltage-gated L-type cardiac calcium channel (Cav1.2) has been involved in the pathogenesis of Timothy syndrome (TS). TS is a variant of the long QT syndrome (also LQT8) and it is a rare and severe genetic disorder characterized by a spectrum of complex phenotypes including QT interval prolongation, congenital heart defects, syndactyly, and distinctive dysmorphic features. So far TS is the only inherited arrhythmogenic disorder linked to cardiac calcium channel mutations. In this chapter, we will briefly review the structure, physiology, and pathophysiology of the cardiac Cav1.2 encoded by the CACNA1c gene.
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