Roles of interstitial cells of Cajal in regulating gastrointestinal motility: in vitro versus in vivo studies

•  Subtypes and functions of ICC in the gut ‐  Subtypes of ICC ‐  ICC along the gut ‐  Functions of ICC•  Mutant animal models used in in vitro and in vivo studies •  Roles of ICC in generating slow waves ‐  Gastrointestinal slow waves and their clinical ‐  significance ‐  In vitro studies ‐  In vivo studies•  Roles of ICC in regulating gastrointestinal motility ‐  Gastrointestinal motility and roles of slow waves ‐  Roles of ICC in regulating peristaltic contractions•  Roles of ICC in mediating neural transmission ‐  In vitro studies ‐  LOS and pylorus sphincter ‐  Stomach ‐  Small intestine ‐  Colon ‐  In vivo studies ‐  Lower oesophageal sphincter ‐  Stomach ‐  Colon ‐  Anal sphincter•  Roles of ICC as mechanoreceptors •  ConclusionsAbstract The aim of this article is to provide a better understanding of the roles of interstitial cells of Cajal (ICC) in regulating gastrointestinal motility by reviewing in vitro and in vivo physiological motility studies. Based on the in vitro studies, ICC are proposed to have the following functions: to generate slow waves, to mediate neurotransmission between the enteric nerves and the gastrointestinal muscles and to act as mechanoreceptors. However, there is limited evidence available for these hypotheses from the in vivo motility studies. In this review, we first introduce the major subtypes of ICC and their established functions. Three Kit mutant mouse and rodent models are presented and the loss of ICC subtypes in these mutants is reviewed. The physiological motility findings from various in vitroand in vivo experiments are discussed to give a critical review on the roles of ICC in generating slow waves, regulating gastrointestinal motility, mediating neural transmission and serving as mechanoreceptors. It is concluded that the role of ICC as pacemakers may be well established, but other cells may also be involved in the generation of slow waves; the theory that ICC are mediators of neurotransmission is challenged by the majority of the in vivo motility studies; the hypothesis that ICC are mechanoreceptors has not found supportive evidence from the in vivo studies yet. More studies are needed to explain discrepancies in motility findings between the in vitro and in vivo experiments.