Cardiac sodium channel variants and gating defects are linked to both inherited arrhythmia syndromes and structural cardiac defects, highlighting the sodium channel as a target for novel therapies.
Inherited arrhythmia syndromes have advanced our understanding of cardiac sodium (Na) channel function in health and disease. Long QT syndrome (LQT3) is consistently caused by increased net Na current secondary to inactivation defects, which give rise to persistent Na current. Conversely, various gating changes that ultimately result in reduced Na current may elicit Brugada syndrome, conduction disease, atrial standstill, and sinus node disease. Emerging insights now also link these gating defects to enhanced arrhythmia susceptibility in common, acquired, disease. For instance, action potential prolongation in congestive heart failure may be explained by increased persistent Na current. Of note, recent studies have also linked Na current reduction to structural cardiac defects, notably cardiac fibrosis, dilated cardiomyopathy and, possibly, arrhythmogenic right ventricular cardiomyopathy. These structural changes may also be conducive to (reentrant) arrhythmias. Clearly, these observations highlight the cardiac Na channel as an interesting target for novel therapy strategies.
Hanno L. Tan (Fri,) conducted a review in Heart Disease and Arrhythmia Syndromes. Cardiac sodium channel variants and gating defects are linked to both inherited arrhythmia syndromes and structural cardiac defects, highlighting the sodium channel as a target for novel therapies.