Chapter 5 - Ion channel defects in primary electrical diseases of the heart

Abstract

The chapter focuses on the ionic basis of cardiac arrhythmia. Abnormal function or expression of cardiac ion channels has the potential for triggering arrhythmia that can result in sudden death. Although most arrhythmias are associated with structural heart diseases, some have been attributed to primary electrical diseases in which malfunctions associated with ion channels play an important role. Correlations between ion channel dysfunction and pathogenesis are made simpler in heart than in nervous system because of well-established relationships between various ionic current components and the cardiac action potential, and between the action potential waveform and rhythmicity; and the identification of specific ion channel genes with observed ionic currents has facilitated the elucidation of genetic components of these disorders. Long-QT syndrome (LQTS) is a serious cardiac disorder that causes loss of consciousness and sudden death in otherwise healthy individuals. A number of inherited defects in cardiac K+ and Na+ channels have been identified as the underlying causes of long QT syndrome, a disease in which malignant ventricular arrhythmia is associated with delayed repolarization phase of the cardiac action potential. The chapter describes the clinical aspects, basic mechanisms, genetic linkages, experimental models, and unresolved issues of LQTS. It highlights the importance of HERG, KvLQT1, LQT2, LQT3, minK, and SCN5A genes in this form of arrhythmia. The chapter briefly describes idiopathic ventricular fibrillation, an aion channel disorder that does not involve reporatization abnormalities.