Recent genetic discoveries implicating ion channels in human cardiovascular diseases

• Exome sequencing has enabled discovery of new channelopathies.
• Mutations in calmodulin have been defined as novel cardiac arrhythmia susceptibility genes.
• A peripheral nerve sodium channel emerged as an important contributor to cardiac conduction.
• Mutations in a twin-pore, acid-sensing potassium channel cause pulmonary artery hypertension.
• Somatic or germline mutations in potassium and calcium channels cause primary aldosteronism.

The term ‘channelopathy’ refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.