VIRTUAL CBAC Seminar: Carol Ann Remme (Academic Medical Center in Amsterdam, Netherlands) – “Sodium channel dysfunction and cardiac arrhythmias – novel mechanisms and therapeutic targets”

April 13, 2021
10:00 am - 11:00 am
Zoom conference (Virtual)

“Sodium channel dysfunction and cardiac arrhythmias – novel mechanisms and therapeutic targets”

Hosted by the Cardiac Bioelectricity and Arrhythmia Center (CBAC)


Abstract: The cardiac sodium channel Nav1.5, encoded by the SCN5A gene, is a key regulator of cardiac conduction, and sodium channel dysfunction may lead to cardiac arrhythmias and sudden cardiac death. Mutations in SCN5A are associated with a myriad of clinical syndromes, including Brugada syndrome, Long QT syndrome type 3, cardiac conduction disease, and overlap syndromes. The underlying mechanisms include a decrease in peak sodium current leading to conduction abnormalities and/or an increase in late sodium current causing repolarization disturbances. Yet, some Nav1.5-related disturbances, in particular structural abnormalities, may not be directly or solely explained on the basis of defective Nav1.5 expression or biophysics. An emerging concept that may explain the large disease spectrum associated with SCN5A mutations centres around the diversity, complexity and multifunctionality of the Nav1.5 complex. For instance, alterations in Nav1.5 may affect processes that are independent of its canonical ion-conducting role, including intracellular homeostasis. In addition, subcellular pools of Nav1.5-based sodium channels within the cardiomyocyte have been demonstrated, in particular at the intercalated disc and lateral membrane regions, where they associate with specific interacting proteins and display distinct functional properties. The trafficking pathways through which sodium channels reach their various subcellular destinations within the cardiomyocyte are now coming into focus. This lecture will address these recent insights and discuss the potential implications for the development of novel therapeutic strategies.

For inquiries contact Huyen Nguyen.