Targeting sodium channels in cardiac arrhythmia

• Acquired and inherited dysfunction of cardiac sodium channels is associated with arrhythmia.
• Peak sodium current inhibition may be pro-arrhythmic in ischemic and structurally abnormal hearts.
• Late sodium current inhibition has anti-arrhythmic potential in heart failure, cardiomyopathy and LQT3.
• Unraveling sodium channel complexity and diversity may identify novel therapeutic targets.

Cardiac voltage-gated sodium channels are responsible for proper electrical conduction in the heart. During acquired pathological conditions and inherited sodium channelopathies, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. Although the clinical, genetic and biophysical characteristics of cardiac sodium channel disease have been extensively studied, limited progress has been made in the development of treatment strategies targeting sodium channels. Classical non-selective sodium channel blockers have only limited clinical applicability, while more selective inhibitors of the late sodium current constitute a more promising treatment option. Because of our insufficient understanding of their complexity and subcellular diversity, other specific therapeutic targets for modulating sodium channels remain elusive. The current status and future potential of targeting sodium channels in cardiac arrhythmias are discussed.