title: 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 Nav 1.5. In the heart, aberrant variants in this sodium channel, encoded by SCN5A, are linked to inherited arrhythmia syndromes, like the long-QT syndrome type 3 and Brugada syndrome. Mounting data show a possible contribution of SCN5A mutants to gastrointestinal functional and motility disorders. Two percent of IBS patients harbor SCN5A mutations with electrophysiological evidence of loss- and gain-of-function. In addition, gastrointestinal symptoms are more prevalent in cardiac SCN5A-mutation positive patients.
  
  
  OBJECTIVE
  This review firstly describes the Nav 1.5 channel and its physiological role in ventricular cardiomyocytes and gastrointestinal cells, then we focus on the involvement of mutant Nav 1.5 in gastrointestinal functional and motility disorders. Future research might uncover novel mutation-specific treatment strategies for SCN5A-encoded gastrointestinal channelopathies.
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: T E
authors.initials: TE
authors.lastname: Verstraelen
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: R M A
authors.initials: RM
authors.lastname: Ter Bekke
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: P G A
authors.initials: PG
authors.lastname: Volders
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: A A M
authors.initials: AA
authors.lastname: Masclee
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Kruimel
mesh_terms: D053447:Channelopathies / Q000378:metabolism* / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: GI motility; SCN5a; genetics; irritable bowel syndrome; voltage-gated sodium channel