The role of the SCN5A‐encoded channelopathy in irritable bowel syndrome and other gastrointestinal disorders

Abstract Background Gastrointestinal functional and motility disorders, like irritable bowel syndrome ( IBS ), have a high prevalence in the Western population and cause significant morbidity and loss of quality of life leading to considerable costs for health care. A decade ago, it has been demonstrated that interstitial cells of Cajal and intestinal smooth muscle cells, cells important for gastrointestinal motility, express the sodium channel alpha subunit Na v 1.5. In the heart, aberrant variants in this sodium channel, encoded by SCN 5A , are linked to inherited arrhythmia syndromes, like the long‐ QT syndrome type 3 and Brugada syndrome. Mounting data show a possible contribution of SCN 5A mutants to gastrointestinal functional and motility disorders. Two percent of IBS patients harbor SCN 5A mutations with electrophysiological evidence of loss‐ and gain‐of‐function. In addition, gastrointestinal symptoms are more prevalent in cardiac SCN 5A ‐mutation positive patients. Purpose This review firstly describes the Na v 1.5 channel and its physiological role in ventricular cardiomyocytes and gastrointestinal cells, then we focus on the involvement of mutant Na v 1.5 in gastrointestinal functional and motility disorders. Future research might uncover novel mutation‐specific treatment strategies for SCN 5A ‐encoded gastrointestinal channelopathies.