MiniReview Gut Pacemaker Cells : the Interstitial Cells of Cajal ( ICC )

This review will focus on the pacemaker mechanisrns underlying gastrointestinal autonomic rhythmicity in an attempt to elucidate the differences and similarities between the pacemaker mechanisrns in the heart and gut. Interstitial cells of Cajal (ICC) form networks that are widely distributed within the submucosal (ICC-SM) , intra-muscular (ICCIM, ICC-DMP) and inter-muscular layers (ICC-MY) of the gastrointestinal tract from the esophagus to the internal anal sphincter. The ICC generate spontaneously active pacemaker currents that may be recorded as plateau and slow potentials. These pacemaker currents drive the spontaneous electrical and mechanical activities of smooth muscle cells. The enteric nervous system, composed of both the myenteric (inteFmuscular) plexus and the submucosal plexus, is also distributed in the gastrointestinal tract from the esophagus to the internal anal sphincter. 'Ihe role of the ICC and the enteric nervous system in the integrative control of gastrointestinal function and especially of spontaneous rhythmic activity, is sti11 unknown, Nevemheless, at least from the results presented in this review of studies of the jejunum, ileum and proximal colon of the mouse, it is convincing that the ICC drive spontaneous rhythmic motility, although a role for the enteric nervous system in the regulation of spontaneous rhythmic motility cannot be overlooked. Furthermore, intracellular C 2' handling has a critical role in the generation of pacemaker activity in the gut and heart, although respective players such as the Ca2'-fYI"Pase of the sarcoplasmic reticulum (endoplasmic reticulum), IP3 receptors, ryanodine receptors and plasma membrane ion channels may have divergent roles in the Ca2"-release r fi11ing cycles. In conclusion, intracellular C 2' handling plays a key role in the gut pacemaker responsible for spontaneous rhytihmicity, as well as in the cardiac pacemaker responsible for spontaneous beating. Pharmacotherapeutic targeting of intracellular Ca2' handling mechanisms may be a promising approach to the treatment and cure of gttt motility dysfunction,